Sepsis-associated acute kidney injury in mice and humans elicits heterogeneous renal microvascular microRNA responses

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Názov: Sepsis-associated acute kidney injury in mice and humans elicits heterogeneous renal microvascular microRNA responses
Autori: Luxen, Matthijs, van der Aart, Tamar J, Jongman, Rianne M, Zwiers, Peter J, Moser, Jill, Pultar, Marianne, Skalicky, Susanna, Diendorfer, Andreas B, Bouma, Hjalmar R, Koeze, Jacqueline, Hackl, Matthias, Molema, Grietje, van Meurs, Matijs
Zdroj: Scientific Reports. 15(1)
Informácie o vydavateľovi: Nature Publishing Group, 2025.
Rok vydania: 2025
Predmety: Male, Acute Kidney Injury/etiology, Kidney/blood supply, Endothelial Cells/metabolism, Middle Aged, Inbred C57BL, MicroRNAs/genetics, Mice, Sepsis/complications, Microvessels/metabolism, Humans, Animals, Female, Biomarkers
Popis: Microvascular endothelial cells play important roles in sepsis-associated acute kidney injury (SA-AKI). In this study, we focused on microvascular microRNAs changes following SA-AKI to identify microRNAs as novel druggable targets and microvasculature-related early biomarkers of SA-AKI. Using small RNA sequencing we identified 40 differentially expressed microRNAs in the renal microvasculature in response to SA-AKI. While the induction of most microRNAs was restricted to a single microvascular compartment, miR-21-5p levels were increased across the renal microvasculature in both mice and humans following SA-AKI. Functional assessment in vitro revealed that inhibition of hsa-miR-21-5p exacerbated endothelial inflammatory activation, suggesting a protective role of this microRNA in endothelial cells. Furthermore, patients with SA-AKI exhibited elevated hsa-miR-21-5p levels in plasma compared with critically ill sepsis patients without AKI. These results highlight the potential of hsa-miR-21-5p and other microRNAs as therapeutic targets and biomarkers in SA-AKI.
Druh dokumentu: Article
Jazyk: English
ISSN: 2045-2322
DOI: 10.1038/s41598-025-17319-0
Prístupová URL adresa: https://research.rug.nl/en/publications/25cdd50c-b58a-4ba9-999e-6c676bfd42c4
https://hdl.handle.net/11370/25cdd50c-b58a-4ba9-999e-6c676bfd42c4
Rights: CC BY NC ND
Prístupové číslo: edsair.dris...01423..741a15d2e8ee7f9637b07c944c0bbf9f
Databáza: OpenAIRE
Popis
Abstrakt:Microvascular endothelial cells play important roles in sepsis-associated acute kidney injury (SA-AKI). In this study, we focused on microvascular microRNAs changes following SA-AKI to identify microRNAs as novel druggable targets and microvasculature-related early biomarkers of SA-AKI. Using small RNA sequencing we identified 40 differentially expressed microRNAs in the renal microvasculature in response to SA-AKI. While the induction of most microRNAs was restricted to a single microvascular compartment, miR-21-5p levels were increased across the renal microvasculature in both mice and humans following SA-AKI. Functional assessment in vitro revealed that inhibition of hsa-miR-21-5p exacerbated endothelial inflammatory activation, suggesting a protective role of this microRNA in endothelial cells. Furthermore, patients with SA-AKI exhibited elevated hsa-miR-21-5p levels in plasma compared with critically ill sepsis patients without AKI. These results highlight the potential of hsa-miR-21-5p and other microRNAs as therapeutic targets and biomarkers in SA-AKI.
ISSN:20452322
DOI:10.1038/s41598-025-17319-0