Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury

Tubulointerstitial inflammation is a common characteristic of acute and chronic kidney injury. However, the mechanism by which the initial injury of tubular epithelial cells (TECs) drives interstitial inflammation remains unclear. This paper aims to explore the role of exosomal miRNAs derived from T...

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Vydáno v:Cell death and differentiation Ročník 27; číslo 1; s. 210 - 226
Hlavní autoři: Lv, Lin-Li, Feng, Ye, Wu, Min, Wang, Bin, Li, Zuo-Lin, Zhong, Xin, Wu, Wei-Jun, Chen, Jun, Ni, Hai-Feng, Tang, Tao-Tao, Tang, Ri-Ning, Lan, Hui-Yao, Liu, Bi-Cheng
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Nature Publishing Group 01.01.2020
Témata:
Acute Kidney Injury - genetics
Acute Kidney Injury - metabolism
Adult
Aged
Animals
Cell activation
Cells, Cultured
Diabetic Nephropathies - urine
Diabetic nephropathy
Epithelial cells
Epithelial Cells - metabolism
Exosomes - genetics
Exosomes - metabolism
Female
Humans
Inflammation
Kidney - metabolism
Kidney - pathology
Kidney diseases
Kidney Tubules - metabolism
Macrophage Activation
Macrophages
Macrophages - metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
MicroRNAs
MicroRNAs - metabolism
MicroRNAs - urine
Middle Aged
miRNA
Nephritis - genetics
Nephritis - pathology
NF-kappa B - metabolism
Proteinuria - chemically induced
Proteinuria - genetics
Proteinuria - metabolism
RAW 264.7 Cells
Suppressor of Cytokine Signaling 1 Protein - genetics
Suppressor of Cytokine Signaling 1 Protein - metabolism
ISSN:1350-9047, 1476-5403, 1476-5403
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Shrnutí:Tubulointerstitial inflammation is a common characteristic of acute and chronic kidney injury. However, the mechanism by which the initial injury of tubular epithelial cells (TECs) drives interstitial inflammation remains unclear. This paper aims to explore the role of exosomal miRNAs derived from TECs in the development of tubulointerstitial inflammation. Global microRNA(miRNA) expression profiling of renal exosomes was examined in a LPS induced acute kidney injury (AKI) mouse model and miR-19b-3p was identified as the miRNA that was most notably increased in TEC-derived exosomes compared to controls. Similar results were also found in an adriamycin (ADR) induced chronic proteinuric kidney disease model in which exosomal miR-19b-3p was markedly released. Interestingly, once released, TEC-derived exosomal miR-19b-3p was internalized by macrophages, leading to M1 phenotype polarization through targeting NF-κB/SOCS-1. A dual-luciferase reporter assay confirmed that SOCS-1 was the direct target of miR-19b-3p. Importantly, the pathogenic role of exosomal miR-19b-3p in initiating renal inflammation was revealed by the ability of adoptively transferred of purified TEC-derived exosomes to cause tubulointerstitial inflammation in mice, which was reversed by inhibition of miR-19b-3p. Clinically, high levels of miR-19b-3p were found in urinary exosomes and were correlated with the severity of tubulointerstitial inflammation in patients with diabetic nephropathy. Thus, our studies demonstrated that exosomal miR-19b-3p mediated the communication between injured TECs and macrophages, leading to M1 macrophage activation. The exosome/miR-19b-3p/SOCS1 axis played a critical pathologic role in tubulointerstitial inflammation, representing a new therapeutic target for kidney disease.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1350-9047
1476-5403
1476-5403
DOI:10.1038/s41418-019-0349-y