RNA-Seq Provides Insights into VEGF-Induced Signaling in Human Retinal Microvascular Endothelial Cells: Implications in Retinopathy of Prematurity

The pathophysiology of retinopathy of prematurity (ROP) is postulated to first involve delayed intraretinal vascularization, followed by intravitreal neovascularization (IVNV). Although intravitreal agents that reduce the bioactivity of vascular endothelial growth factor (VEGF) are used to treat IVN...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	International journal of molecular sciences Ročník 23; číslo 13; s. 7354
Hlavní autori:	Ramshekar, Aniket, Bretz, Colin A., Hartnett, M. Elizabeth
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Switzerland MDPI AG 01.07.2022 MDPI
Predmet:	Angiogenesis Animals Datasets Disease Models, Animal Endothelial Cells - metabolism Gene expression Humans Hypotheses Infant, Newborn Neovascularization, Pathologic - metabolism Rats Rats, Sprague-Dawley Retinal Neovascularization - metabolism Retinal Vessels - metabolism Retinopathy of Prematurity - genetics Retinopathy of Prematurity - metabolism RNA-Seq Signal Transduction Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism VEGFR2 ROP RNA-seq HRMECs VEGF STAT3 KDR
ISSN:	1422-0067, 1661-6596, 1422-0067
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Abstract	The pathophysiology of retinopathy of prematurity (ROP) is postulated to first involve delayed intraretinal vascularization, followed by intravitreal neovascularization (IVNV). Although intravitreal agents that reduce the bioactivity of vascular endothelial growth factor (VEGF) are used to treat IVNV, concerns exist regarding their effects on intraretinal vascularization. In an experimental ROP model, VEGF receptor 2 (VEGFR2) knockdown in retinal endothelial cells reduced IVNV and promoted intraretinal vascularization, whereas knockdown of a downstream effector, signal transducer and activator of transcription 3 (STAT3) in retinal endothelial cells only reduced IVNV. In this study, we tested the hypothesis that the different pathways involved in VEGF-triggered VEGFR2 signaling and VEGF-triggered STAT3 signaling in retinal endothelial cells would allow us to delineate signaling pathways involved in IVNV from those involved in intraretinal vascularization in ROP. To address our hypothesis, we used RNA-sequencing and pathway enrichment analysis to determine changes in the transcriptome of cultured human retinal microvascular endothelial cells (HRMECs). Of the enriched pathways, inactivation of oncostatin M signaling was predicted by either KDR or STAT3 knockdown in the presence of VEGF. Activation of kinetochore metaphase signaling was predicted by KDR knockdown, whereas inactivation was predicted by STAT3 knockdown in the presence of VEGF. Inactivation of signaling by the Rho family of GTPases was predicted by KDR knockdown, but activation was predicted by STAT3 knockdown in the presence of VEGF. Taken together, our data identified unique signaling pathway differences between VEGF-triggered VEGFR2 and VEGF-triggered STAT3 in HRMECs that might have implications in ROP.
AbstractList	The pathophysiology of retinopathy of prematurity (ROP) is postulated to first involve delayed intraretinal vascularization, followed by intravitreal neovascularization (IVNV). Although intravitreal agents that reduce the bioactivity of vascular endothelial growth factor (VEGF) are used to treat IVNV, concerns exist regarding their effects on intraretinal vascularization. In an experimental ROP model, VEGF receptor 2 (VEGFR2) knockdown in retinal endothelial cells reduced IVNV and promoted intraretinal vascularization, whereas knockdown of a downstream effector, signal transducer and activator of transcription 3 (STAT3) in retinal endothelial cells only reduced IVNV. In this study, we tested the hypothesis that the different pathways involved in VEGF-triggered VEGFR2 signaling and VEGF-triggered STAT3 signaling in retinal endothelial cells would allow us to delineate signaling pathways involved in IVNV from those involved in intraretinal vascularization in ROP. To address our hypothesis, we used RNA-sequencing and pathway enrichment analysis to determine changes in the transcriptome of cultured human retinal microvascular endothelial cells (HRMECs). Of the enriched pathways, inactivation of oncostatin M signaling was predicted by either KDR or STAT3 knockdown in the presence of VEGF. Activation of kinetochore metaphase signaling was predicted by KDR knockdown, whereas inactivation was predicted by STAT3 knockdown in the presence of VEGF. Inactivation of signaling by the Rho family of GTPases was predicted by KDR knockdown, but activation was predicted by STAT3 knockdown in the presence of VEGF. Taken together, our data identified unique signaling pathway differences between VEGF-triggered VEGFR2 and VEGF-triggered STAT3 in HRMECs that might have implications in ROP. The pathophysiology of retinopathy of prematurity (ROP) is postulated to first involve delayed intraretinal vascularization, followed by intravitreal neovascularization (IVNV). Although intravitreal agents that reduce the bioactivity of vascular endothelial growth factor (VEGF) are used to treat IVNV, concerns exist regarding their effects on intraretinal vascularization. In an experimental ROP model, VEGF receptor 2 (VEGFR2) knockdown in retinal endothelial cells reduced IVNV and promoted intraretinal vascularization, whereas knockdown of a downstream effector, signal transducer and activator of transcription 3 (STAT3) in retinal endothelial cells only reduced IVNV. In this study, we tested the hypothesis that the different pathways involved in VEGF-triggered VEGFR2 signaling and VEGF-triggered STAT3 signaling in retinal endothelial cells would allow us to delineate signaling pathways involved in IVNV from those involved in intraretinal vascularization in ROP. To address our hypothesis, we used RNA-sequencing and pathway enrichment analysis to determine changes in the transcriptome of cultured human retinal microvascular endothelial cells (HRMECs). Of the enriched pathways, inactivation of oncostatin M signaling was predicted by either KDR or STAT3 knockdown in the presence of VEGF. Activation of kinetochore metaphase signaling was predicted by KDR knockdown, whereas inactivation was predicted by STAT3 knockdown in the presence of VEGF. Inactivation of signaling by the Rho family of GTPases was predicted by KDR knockdown, but activation was predicted by STAT3 knockdown in the presence of VEGF. Taken together, our data identified unique signaling pathway differences between VEGF-triggered VEGFR2 and VEGF-triggered STAT3 in HRMECs that might have implications in ROP.The pathophysiology of retinopathy of prematurity (ROP) is postulated to first involve delayed intraretinal vascularization, followed by intravitreal neovascularization (IVNV). Although intravitreal agents that reduce the bioactivity of vascular endothelial growth factor (VEGF) are used to treat IVNV, concerns exist regarding their effects on intraretinal vascularization. In an experimental ROP model, VEGF receptor 2 (VEGFR2) knockdown in retinal endothelial cells reduced IVNV and promoted intraretinal vascularization, whereas knockdown of a downstream effector, signal transducer and activator of transcription 3 (STAT3) in retinal endothelial cells only reduced IVNV. In this study, we tested the hypothesis that the different pathways involved in VEGF-triggered VEGFR2 signaling and VEGF-triggered STAT3 signaling in retinal endothelial cells would allow us to delineate signaling pathways involved in IVNV from those involved in intraretinal vascularization in ROP. To address our hypothesis, we used RNA-sequencing and pathway enrichment analysis to determine changes in the transcriptome of cultured human retinal microvascular endothelial cells (HRMECs). Of the enriched pathways, inactivation of oncostatin M signaling was predicted by either KDR or STAT3 knockdown in the presence of VEGF. Activation of kinetochore metaphase signaling was predicted by KDR knockdown, whereas inactivation was predicted by STAT3 knockdown in the presence of VEGF. Inactivation of signaling by the Rho family of GTPases was predicted by KDR knockdown, but activation was predicted by STAT3 knockdown in the presence of VEGF. Taken together, our data identified unique signaling pathway differences between VEGF-triggered VEGFR2 and VEGF-triggered STAT3 in HRMECs that might have implications in ROP. The pathophysiology of retinopathy of prematurity (ROP) is postulated to first involve delayed intraretinal vascularization, followed by intravitreal neovascularization (IVNV). Although intravitreal agents that reduce the bioactivity of vascular endothelial growth factor (VEGF) are used to treat IVNV, concerns exist regarding their effects on intraretinal vascularization. In an experimental ROP model, VEGF receptor 2 (VEGFR2) knockdown in retinal endothelial cells reduced IVNV and promoted intraretinal vascularization, whereas knockdown of a downstream effector, signal transducer and activator of transcription 3 (STAT3) in retinal endothelial cells only reduced IVNV. In this study, we tested the hypothesis that the different pathways involved in VEGF-triggered VEGFR2 signaling and VEGF-triggered STAT3 signaling in retinal endothelial cells would allow us to delineate signaling pathways involved in IVNV from those involved in intraretinal vascularization in ROP. To address our hypothesis, we used RNA-sequencing and pathway enrichment analysis to determine changes in the transcriptome of cultured human retinal microvascular endothelial cells (HRMECs). Of the enriched pathways, inactivation of oncostatin M signaling was predicted by either or knockdown in the presence of VEGF. Activation of kinetochore metaphase signaling was predicted by knockdown, whereas inactivation was predicted by knockdown in the presence of VEGF. Inactivation of signaling by the Rho family of GTPases was predicted by knockdown, but activation was predicted by knockdown in the presence of VEGF. Taken together, our data identified unique signaling pathway differences between VEGF-triggered VEGFR2 and VEGF-triggered STAT3 in HRMECs that might have implications in ROP.
Author	Hartnett, M. Elizabeth Ramshekar, Aniket Bretz, Colin A.
AuthorAffiliation	Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Dr, Salt Lake City, UT 84132, USA; u1088294@utah.edu (A.R.); u6003023@utah.edu (C.A.B.)
AuthorAffiliation_xml	– name: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Dr, Salt Lake City, UT 84132, USA; u1088294@utah.edu (A.R.); u6003023@utah.edu (C.A.B.)
Author_xml	– sequence: 1 givenname: Aniket surname: Ramshekar fullname: Ramshekar, Aniket – sequence: 2 givenname: Colin A. surname: Bretz fullname: Bretz, Colin A. – sequence: 3 givenname: M. Elizabeth surname: Hartnett fullname: Hartnett, M. Elizabeth
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/35806359$$D View this record in MEDLINE/PubMed
BookMark	eNptkk1vGyEQhlGVqvlobz1XSL300E1ZYMHbQ6XIchJL6YeSqFdEgLXH2gUH2Ej-G_3FIXFSuVFPIOaZd4Z35hDt-eAdQu9rcsxYS77AakiU1Uyyhr9CBzWntCJEyL2d-z46TGlFCGW0ad-gfdZMiGBNe4D-XP44qa7cLf4Vwx1Yl_DcJ1gsc8Lgc8C_Z2en1dzb0TiLr2DhdQ9-UWL4fBy0x5cuQ3nD38EUAZ3M2OuIZ96GvHQ9lMjU9X36iufDugejMwT_IL1NDGudlxsculLeDTqPEfLmLXrd6T65d0_nEbo-nV1Pz6uLn2fz6clFZXhNc0VN23FpRcOotZZpYTrNmNCcOlLMsPLG1FpMGHeE1q2hXDTEStkZRvmEtewIfdvKrsebwVnjfI66V-sIg44bFTSofyMelmoR7lRLheCcFYFPTwIx3I4uZTVAMuW32rswJkXFREraMCEL-vEFugpjLL49UqIu8yO8UB92O_rbyvO0CkC3QPE6peg6ZSA_WloahF7VRD2shNpdiZL0-UXSs-5_8Xu4ELnA
CitedBy_id	crossref_primary_10_1038_s41598_025_87205_2 crossref_primary_10_1146_annurev_vision_093022_021420 crossref_primary_10_1186_s13619_025_00223_3 crossref_primary_10_1096_fba_2025_00146 crossref_primary_10_1038_s41598_023_30568_1 crossref_primary_10_3892_etm_2025_12893 crossref_primary_10_3389_fped_2024_1382858
Cites_doi	10.1016/j.ajpath.2011.11.031 10.1038/s41598-021-94500-1 10.1038/nrm.2016.87 10.1038/nm0603-669 10.1038/s41390-020-0793-x 10.1038/s41390-019-0598-y 10.1001/jamaophthalmol.2022.0030 10.1016/j.cmet.2021.01.011 10.3389/fped.2021.796143 10.1038/s41598-018-20278-4 10.1056/NEJMoa1007374 10.1172/jci.insight.129224 10.1167/iovs.01-1193 10.1056/NEJMra1208129 10.3109/02713683.2011.593110 10.1001/archophthalmol.2012.592 10.1159/000364809 10.5301/ejo.5000166 10.1136/bjo.2008.140657 10.1016/j.earlhumdev.2007.11.009 10.1016/j.jaapos.2013.01.004 10.1001/archopht.121.12.1684 10.1371/journal.pone.0003554 10.1167/iovs.13-13755 10.1203/00006450-199412000-00007 10.1136/bjophthalmol-2012-302276 10.1167/iovs.14-14217 10.1371/journal.pone.0045858 10.1093/bioinformatics/btt703 10.3928/23258160-20160229-12 10.1186/s13059-014-0550-8 10.1167/iovs.08-3256 10.1007/s10456-018-9618-5
ContentType	Journal Article
Copyright	2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2022 by the authors. 2022
Copyright_xml	– notice: 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2022 by the authors. 2022
DBID	AAYXX CITATION CGR CUY CVF ECM EIF NPM 3V. 7X7 7XB 88E 8FI 8FJ 8FK 8G5 ABUWG AFKRA AZQEC BENPR CCPQU DWQXO FYUFA GHDGH GNUQQ GUQSH K9. M0S M1P M2O MBDVC PHGZM PHGZT PIMPY PJZUB PKEHL PPXIY PQEST PQQKQ PQUKI PRINS Q9U 7X8 5PM
DOI	10.3390/ijms23137354
DatabaseName	CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed ProQuest Central (Corporate) Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) Research Library (Alumni Edition) ProQuest Central (Alumni Edition) ProQuest Central UK/Ireland ProQuest Central Essentials ProQuest Central ProQuest One Community College ProQuest Central Korea Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student Research Library Prep ProQuest Health & Medical Complete (Alumni) Health & Medical Collection (Alumni Edition) Medical Database Research Library Research Library (Corporate) ProQuest Central Premium ProQuest One Academic (New) Publicly Available Content Database (ProQuest) ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic (retired) ProQuest One Academic UKI Edition ProQuest Central China ProQuest Central Basic MEDLINE - Academic PubMed Central (Full Participant titles)
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Publicly Available Content Database Research Library Prep ProQuest Central Student ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) ProQuest One Community College ProQuest One Health & Nursing Research Library (Alumni Edition) ProQuest Central China ProQuest Central ProQuest Health & Medical Research Collection Health Research Premium Collection Health and Medicine Complete (Alumni Edition) ProQuest Central Korea Health & Medical Research Collection ProQuest Research Library ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest Central Basic ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) ProQuest Hospital Collection (Alumni) ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic
DatabaseTitleList	Publicly Available Content Database CrossRef MEDLINE - Academic MEDLINE
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: PIMPY name: Publicly Available Content Database url: http://search.proquest.com/publiccontent sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Biology
EISSN	1422-0067
ExternalDocumentID	PMC9266443 35806359 10_3390_ijms23137354
Genre	Journal Article
GrantInformation_xml	– fundername: NEI NIH HHS grantid: P30 EY014800 – fundername: NEI NIH HHS grantid: F30 EY032311 – fundername: NEI NIH HHS grantid: T32 EY024234 – fundername: NEI NIH HHS grantid: F30EY032311 – fundername: NEI NIH HHS grantid: P30EY014800 – fundername: NEI NIH HHS grantid: R01EY015130 – fundername: Research to Prevent Blindness grantid: N/A – fundername: NEI NIH HHS grantid: R01 EY017011 – fundername: NEI NIH HHS grantid: R01EY017011 – fundername: NEI NIH HHS grantid: R01 EY015130 – fundername: National Institutes of Health/National Eye Institute grantid: R01EY015130; R01EY017011; F30EY032311 – fundername: Research to Prevent Blindness – fundername: National Institutes of Health Core grantid: P30EY014800
GroupedDBID	--- 29J 2WC 53G 5GY 5VS 7X7 88E 8FE 8FG 8FH 8FI 8FJ 8G5 A8Z AADQD AAFWJ AAHBH AAYXX ABDBF ABUWG ACGFO ACIHN ACIWK ACPRK ACUHS ADBBV AEAQA AENEX AFFHD AFKRA AFZYC ALMA_UNASSIGNED_HOLDINGS AOIJS AZQEC BAWUL BCNDV BENPR BPHCQ BVXVI CCPQU CITATION CS3 D1I DIK DU5 DWQXO E3Z EBD EBS EJD ESX F5P FRP FYUFA GNUQQ GUQSH GX1 HH5 HMCUK HYE IAO IHR ITC KQ8 LK8 M1P M2O M48 MODMG O5R O5S OK1 OVT P2P PHGZM PHGZT PIMPY PJZUB PPXIY PQQKQ PROAC PSQYO RNS RPM TR2 TUS UKHRP ~8M ALIPV CGR CUY CVF ECM EIF NPM 3V. 7XB 8FK ESTFP K9. MBDVC PKEHL PQEST PQUKI PRINS Q9U 7X8 PUEGO 5PM
ID	FETCH-LOGICAL-c412t-2c9f47d6532ddd3a6cfa336a42e0373d7bc1a6834e0219c24650d77fc3248393
IEDL.DBID	BENPR
ISICitedReferencesCount	9
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000825646700001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	1422-0067 1661-6596
IngestDate	Tue Nov 04 01:56:29 EST 2025 Fri Sep 05 07:52:54 EDT 2025 Tue Oct 07 07:42:56 EDT 2025 Thu Apr 03 06:58:08 EDT 2025 Sat Nov 29 07:16:56 EST 2025 Tue Nov 18 21:37:25 EST 2025
IsDoiOpenAccess	true
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	13
Keywords	VEGFR2 ROP RNA-seq HRMECs VEGF STAT3 KDR
Language	English
License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c412t-2c9f47d6532ddd3a6cfa336a42e0373d7bc1a6834e0219c24650d77fc3248393
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
OpenAccessLink	https://www.proquest.com/docview/2686123104?pq-origsite=%requestingapplication%
PMID	35806359
PQID	2686123104
PQPubID	2032341
ParticipantIDs	pubmedcentral_primary_oai_pubmedcentral_nih_gov_9266443 proquest_miscellaneous_2687725367 proquest_journals_2686123104 pubmed_primary_35806359 crossref_citationtrail_10_3390_ijms23137354 crossref_primary_10_3390_ijms23137354
PublicationCentury	2000
PublicationDate	2022-07-01 2022-Jul-01 20220701
PublicationDateYYYYMMDD	2022-07-01
PublicationDate_xml	– month: 07 year: 2022 text: 2022-07-01 day: 01
PublicationDecade	2020
PublicationPlace	Switzerland
PublicationPlace_xml	– name: Switzerland – name: Basel
PublicationTitle	International journal of molecular sciences
PublicationTitleAlternate	Int J Mol Sci
PublicationYear	2022
Publisher	MDPI AG MDPI
Publisher_xml	– name: MDPI AG – name: MDPI
References	Shaw (ref_27) 2019; 4 Bullard (ref_30) 2003; 44 Castellanos (ref_21) 2013; 97 Penn (ref_13) 1994; 36 Ittiara (ref_6) 2013; 17 Tsuruda (ref_25) 2021; 33 Gilbert (ref_1) 2008; 84 Zasada (ref_26) 2020; 88 ref_32 Kennedy (ref_4) 2011; 364 Snyder (ref_7) 2016; 47 Zasada (ref_31) 2020; 87 Simons (ref_12) 2016; 17 Kramer (ref_36) 2014; 30 Autrata (ref_22) 2012; 22 Byfield (ref_16) 2009; 50 Jaszai (ref_28) 2021; 11 Wang (ref_15) 2012; 180 Ramshekar (ref_18) 2021; 9 Love (ref_35) 2014; 15 Kusaka (ref_19) 2008; 92 Hartnett (ref_2) 2012; 367 ref_24 Suarez (ref_34) 2014; 55 Salman (ref_23) 2015; 53 Simmons (ref_14) 2018; 21 ref_3 Hu (ref_5) 2012; 130 Sheng (ref_17) 2017; 16 Fang (ref_33) 2011; 36 ref_8 Arambulo (ref_20) 2015; 9 Ferrara (ref_11) 2003; 9 Jiang (ref_10) 2014; 55 Smith (ref_29) 1994; 35 Becker (ref_9) 2018; 8
References_xml	– volume: 180 start-page: 1243 year: 2012 ident: ref_15 article-title: VEGF-mediated STAT3 activation inhibits retinal vascularization by down-regulating local erythropoietin expression publication-title: Am. J. Pathol. doi: 10.1016/j.ajpath.2011.11.031 – volume: 11 start-page: 15313 year: 2021 ident: ref_28 article-title: Gene expression profile of the murine ischemic retina and its response to Aflibercept (VEGF-Trap) publication-title: Sci. Rep. doi: 10.1038/s41598-021-94500-1 – volume: 17 start-page: 611 year: 2016 ident: ref_12 article-title: Mechanisms and regulation of endothelial VEGF receptor signalling publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm.2016.87 – volume: 9 start-page: 669 year: 2003 ident: ref_11 article-title: The biology of VEGF and its receptors publication-title: Nat. Med. doi: 10.1038/nm0603-669 – volume: 35 start-page: 101 year: 1994 ident: ref_29 article-title: Oxygen-induced retinopathy in the mouse publication-title: Investig. Ophthalmol. Vis. Sci. – volume: 88 start-page: 391 year: 2020 ident: ref_26 article-title: Transcriptome analysis reveals dysregulation of genes involved in oxidative phosphorylation in a murine model of retinopathy of prematurity publication-title: Pediatr. Res. doi: 10.1038/s41390-020-0793-x – volume: 87 start-page: 485 year: 2020 ident: ref_31 article-title: Short- and long-term impact of hyperoxia on the blood and retinal cells’ transcriptome in a mouse model of oxygen-induced retinopathy publication-title: Pediatr. Res. doi: 10.1038/s41390-019-0598-y – ident: ref_24 doi: 10.1001/jamaophthalmol.2022.0030 – volume: 33 start-page: 818 year: 2021 ident: ref_25 article-title: Pathological angiogenesis in retinopathy engages cellular senescence and is amenable to therapeutic elimination via BCL-xL inhibition publication-title: Cell Metab. doi: 10.1016/j.cmet.2021.01.011 – volume: 9 start-page: 796143 year: 2021 ident: ref_18 article-title: Vascular Endothelial Growth Factor Signaling in Models of Oxygen-Induced Retinopathy: Insights into Mechanisms of Pathology in Retinopathy of Prematurity publication-title: Front. Pediatr. doi: 10.3389/fped.2021.796143 – volume: 8 start-page: 2003 year: 2018 ident: ref_9 article-title: Targeted Knockdown of Overexpressed VEGFA or VEGF164 in Muller cells maintains retinal function by triggering different signaling mechanisms publication-title: Sci. Rep. doi: 10.1038/s41598-018-20278-4 – volume: 364 start-page: 603 year: 2011 ident: ref_4 article-title: Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1007374 – volume: 4 start-page: e129224 year: 2019 ident: ref_27 article-title: Progenitor cell combination normalizes retinal vascular development in the oxygen-induced retinopathy (OIR) model publication-title: JCI Insight doi: 10.1172/jci.insight.129224 – volume: 44 start-page: 1722 year: 2003 ident: ref_30 article-title: Role for Extracellular Signal-Responsive Kinase-1 and -2 in Retinal Angiogenesis publication-title: Investig. Ophthalmol. Vis. Sci. doi: 10.1167/iovs.01-1193 – volume: 367 start-page: 2515 year: 2012 ident: ref_2 article-title: Mechanisms and management of retinopathy of prematurity publication-title: N. Engl. J. Med. doi: 10.1056/NEJMra1208129 – volume: 36 start-page: 1028 year: 2011 ident: ref_33 article-title: RhoA activation and effect of Rho-kinase inhibitor in the development of retinal neovascularization in a mouse model of oxygen-induced retinopathy publication-title: Curr. Eye Res. doi: 10.3109/02713683.2011.593110 – volume: 130 start-page: 1000 year: 2012 ident: ref_5 article-title: Reactivation of retinopathy of prematurity after bevacizumab injection publication-title: Arch. Ophthalmol. doi: 10.1001/archophthalmol.2012.592 – volume: 53 start-page: 15 year: 2015 ident: ref_23 article-title: Structural, visual and refractive outcomes of intravitreal aflibercept injection in high-risk prethreshold type 1 retinopathy of prematurity publication-title: Ophthalmic Res. doi: 10.1159/000364809 – volume: 22 start-page: 687 year: 2012 ident: ref_22 article-title: Intravitreal pegaptanib combined with diode laser therapy for stage 3+ retinopathy of prematurity in zone I and posterior zone II publication-title: Eur. J. Ophthalmol. doi: 10.5301/ejo.5000166 – volume: 16 start-page: 194 year: 2017 ident: ref_17 article-title: Multi-perspective quality control of Illumina RNA sequencing data analysis publication-title: Brief Funct. Genom. – volume: 92 start-page: 1450 year: 2008 ident: ref_19 article-title: Efficacy of intravitreal injection of bevacizumab for severe retinopathy of prematurity: A pilot study publication-title: Br. J. Ophthalmol. doi: 10.1136/bjo.2008.140657 – volume: 84 start-page: 77 year: 2008 ident: ref_1 article-title: Retinopathy of prematurity: A global perspective of the epidemics, population of babies at risk and implications for control publication-title: Early Hum. Dev. doi: 10.1016/j.earlhumdev.2007.11.009 – volume: 17 start-page: 323 year: 2013 ident: ref_6 article-title: Exudative retinopathy and detachment: A late reactivation of retinopathy of prematurity after intravitreal bevacizumab publication-title: J. Am. Assoc. Pediatr. Ophthalmol. Strabismus doi: 10.1016/j.jaapos.2013.01.004 – ident: ref_3 doi: 10.1001/archopht.121.12.1684 – ident: ref_8 doi: 10.1371/journal.pone.0003554 – volume: 55 start-page: 824 year: 2014 ident: ref_10 article-title: Targeting Muller cell-derived VEGF164 to reduce intravitreal neovascularization in the rat model of retinopathy of prematurity publication-title: Investig. Ophthalmol. Vis. Sci. doi: 10.1167/iovs.13-13755 – volume: 36 start-page: 724 year: 1994 ident: ref_13 article-title: Exposure to alternating hypoxia and hyperoxia causes severe proliferative retinopathy in the newborn rat publication-title: Pediatr. Res. doi: 10.1203/00006450-199412000-00007 – volume: 97 start-page: 816 year: 2013 ident: ref_21 article-title: Short-term outcome after intravitreal ranibizumab injections for the treatment of retinopathy of prematurity publication-title: Br. J. Ophthalmol. doi: 10.1136/bjophthalmol-2012-302276 – volume: 55 start-page: 8232 year: 2014 ident: ref_34 article-title: Modulation of VEGF-induced retinal vascular permeability by peroxisome proliferator-activated receptor-beta/delta publication-title: Investig. Ophthalmol. Vis. Sci. doi: 10.1167/iovs.14-14217 – ident: ref_32 doi: 10.1371/journal.pone.0045858 – volume: 30 start-page: 523 year: 2014 ident: ref_36 article-title: Causal analysis approaches in Ingenuity Pathway Analysis publication-title: Bioinformatics doi: 10.1093/bioinformatics/btt703 – volume: 47 start-page: 280 year: 2016 ident: ref_7 article-title: Very Late Reactivation of Retinopathy of Prematurity after Monotherapy with Intravitreal Bevacizumab publication-title: Ophthalmic Surg. Lasers Imaging Retina doi: 10.3928/23258160-20160229-12 – volume: 15 start-page: 550 year: 2014 ident: ref_35 article-title: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 publication-title: Genome Biol. doi: 10.1186/s13059-014-0550-8 – volume: 9 start-page: 2027 year: 2015 ident: ref_20 article-title: Intravitreal ranibizumab as a primary or a combined treatment for severe retinopathy of prematurity publication-title: Clin. Ophthalmol. – volume: 50 start-page: 3360 year: 2009 ident: ref_16 article-title: The role of supplemental oxygen and JAK/STAT signaling in intravitreous neovascularization in a ROP rat model publication-title: Investig. Ophthalmol. Vis. Sci. doi: 10.1167/iovs.08-3256 – volume: 21 start-page: 751 year: 2018 ident: ref_14 article-title: Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy publication-title: Angiogenesis doi: 10.1007/s10456-018-9618-5
SSID	ssj0023259
Score	2.3965898
Snippet	The pathophysiology of retinopathy of prematurity (ROP) is postulated to first involve delayed intraretinal vascularization, followed by intravitreal...
SourceID	pubmedcentral proquest pubmed crossref
SourceType	Open Access Repository Aggregation Database Index Database Enrichment Source
StartPage	7354
SubjectTerms	Angiogenesis Animals Datasets Disease Models, Animal Endothelial Cells - metabolism Gene expression Humans Hypotheses Infant, Newborn Neovascularization, Pathologic - metabolism Rats Rats, Sprague-Dawley Retinal Neovascularization - metabolism Retinal Vessels - metabolism Retinopathy of Prematurity - genetics Retinopathy of Prematurity - metabolism RNA-Seq Signal Transduction Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism
Title	RNA-Seq Provides Insights into VEGF-Induced Signaling in Human Retinal Microvascular Endothelial Cells: Implications in Retinopathy of Prematurity
URI	https://www.ncbi.nlm.nih.gov/pubmed/35806359 https://www.proquest.com/docview/2686123104 https://www.proquest.com/docview/2687725367 https://pubmed.ncbi.nlm.nih.gov/PMC9266443
Volume	23
WOSCitedRecordID	wos000825646700001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 1422-0067 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0023259 issn: 1422-0067 databaseCode: 7X7 dateStart: 20000301 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: eissn: 1422-0067 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0023259 issn: 1422-0067 databaseCode: BENPR dateStart: 20000301 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest – providerCode: PRVPQU databaseName: Publicly Available Content Database customDbUrl: eissn: 1422-0067 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0023259 issn: 1422-0067 databaseCode: PIMPY dateStart: 20000301 isFulltext: true titleUrlDefault: http://search.proquest.com/publiccontent providerName: ProQuest – providerCode: PRVPQU databaseName: Research Library customDbUrl: eissn: 1422-0067 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0023259 issn: 1422-0067 databaseCode: M2O dateStart: 20000301 isFulltext: true titleUrlDefault: https://search.proquest.com/pqrl providerName: ProQuest
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Lb9NAEB7RFCQuvAuGUi0SnJBVZ3fttbmgUiWQQ4KVViicImd3XYyC3dYpUv8Gv5iZtWMSEFy4WFrtU559fLMzOx_Ay0gbES5M4GshhS8tqjuZFNoPFirkeAQau4gd2YSaTOLZLEnbC7e6datc74luozaVpjvyQx7FFCkEtYe35xc-sUaRdbWl0NiBXYpUJnuw-24wSaedyiW4o0vr4ynkR2ESNa7vAhX9w-LrtxrbE0qEcvtQ-gNp_u4wuXECDe_-79jvwZ0We7KjZrLchxu2fAC3GjbK64fwYzo58k_sBUub13k1G5U16e41K8pVxT4N3g99ovrQ1rCT4owgfHmGecxZAtiUXk9j-2Py8Vt7uLJBaeiR1xLnOTu2y2X9ho02vNipuqtYETfyNaty7J7iyDpWvUdwOhycHn_wW8oGX8s-X_lcJ7lUJgoFN8aILNJ5JkSUSW4D_NNGLXQ_i2IhLWKLRHOJANEolWvEdQjVxB70yqq0T4DlUua5FLnW3Eit4kyEuTGZTAJjTZAEHrxei2yu23DmxKqxnKNaQwKebwrYg1dd6fMmjMdfyu2vJThvF3M9_yU-D1502bgMybaSlba6cmVQTwlFpDx43EyWriOyNCOuSzxQW9OoK0AhvrdzyuKLC_WdIH6SUjz997CewW1OrzKcF_E-9FaXV_Y53NTfV0V9eQA7aqbcNz5o1wemxvwjptLROP38E-FGHZw
linkProvider	ProQuest
linkToHtml	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1bb9MwFD4aHQheuDMCA4zEnpC11HbiBAmhabSs2lpVW4XGU5TazhZUkm3pQP0b_A_-I8e50YLgbQ8827Et57PPOT6XD-CVrzT3ptqligtOhUFzJxZcUXcqPYYiUJtpUJJNyNEoOD4Ox2vwo8mFsWGVzZ1YXtQ6V_aNfJv5ga0UgtbDu7NzalmjrHe1odCoYLFvFt_QZCveDt7j_91irN-b7O7RmlWAKtFlc8pUmAipfY8zrTWPfZXEnPuxYMblkms5Vd3YD7gwKP5CxQTqMFrKRKHqgdoEx2GvwbpArAcdWB8PhuNPrYXHWcnO1kWhR30v9KtIe85Ddzv9_KXA5eMMnliVgX8otr_HZy4JvP6d_2yr7sLtWrMmO9VRuAdrJrsPNyquzcUD-H442qFH5pyMq9zDggyywr5MFCTN5jn52PvQp5bIRBlNjtITa6BkJ9hGSj8HObS54Tj-0EYwNvG7pJdpm8I2w1NMds1sVrwhg6UYfft5-WFumZ8XJE9welslt-QMfAiTq9iPR9DJ8sw8BpIIkSSCJ0oxLZQMYu4lWscidLXRbug68LpBSKTqYu2WM2QWodFm8RQt48mBrbb3WVWk5C_9NhvARPVVVUS_0OLAy7YZLxnrOYozk1-WfdAK87gvHdiosNlOZP3oqLWGDsgV1LYdbAHz1ZYsPS0LmYeoHQrBn_x7WS_g5t5keBAdDEb7T-EWs_knZbz0JnTmF5fmGVxXX-dpcfG8Po4EoitG9U-Yh3OO
linkToPdf	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V3bbtQwEB2VchEv3C-BAkaiTyjarO3ECRJCVbsLq8Kyaquqb1HWdkrQkrTNFrS_wd_wd8zkxi4I3vrAsx3nduyZsc_MAXgRaCP8qfFcLaRwpcVwJ5FCu95U-RxNoLHTsBKbUONxeHQUTdbgR5sLQ7TKdk2sFmpTaNoj7_EgpEohGD300oYWMdkZvjk5dUlBik5aWzmNGiK7dvENw7fy9WgH__Um58PBwfY7t1EYcLXs87nLdZRKZQJfcGOMSAKdJkIEieTWE0oYNdX9JAiFtGgKI80l-jNGqVSjG4KehcBhL8FlJdEmE2uQf-xiPcErnbY-mj838KOg5twLEXm97POXEl8Ex_flqjX8w8X9nam5ZPqGN__jj3YLbjT-NtuqJ8htWLP5HbhaK3Au7sL3vfGWu29P2aTOSCzZKC9pv6JkWT4v2OHg7dAleRNtDdvPjilsyY-xjVWnH2yPMsZx_A_Ea2xZvWyQG0psm-HcZtt2NitfsdESc58ury4sSA96wYoUb0-1cyslwXtwcBHf4z6s50VuHwJLpUxTKVKtuZFahYnwU2MSGXnGGi_yHHjZoiXWTQl3UhKZxRjKEbbiZWw5sNn1PqlLl_yl30YLnrhZwMr4F3IceN4149JD50lJbovzqg_GZr4IlAMPapx2N6LTdfRlIwfUCoK7DlTWfLUlzz5V5c0j9BmlFI_-_VjP4BpCOX4_Gu8-huucklIqEvUGrM_Pzu0TuKK_zrPy7Gk1LxnEFwzpnxMJesg
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=RNA-Seq+Provides+Insights+into+VEGF-Induced+Signaling+in+Human+Retinal+Microvascular+Endothelial+Cells%3A+Implications+in+Retinopathy+of+Prematurity&rft.jtitle=International+journal+of+molecular+sciences&rft.au=Ramshekar%2C+Aniket&rft.au=Bretz%2C+Colin+A.&rft.au=Hartnett%2C+M.+Elizabeth&rft.date=2022-07-01&rft.issn=1422-0067&rft.eissn=1422-0067&rft.volume=23&rft.issue=13&rft.spage=7354&rft_id=info:doi/10.3390%2Fijms23137354&rft.externalDBID=n%2Fa&rft.externalDocID=10_3390_ijms23137354
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1422-0067&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1422-0067&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1422-0067&client=summon