Inhibition of TGF-β 1 Signaling by IL-15: A Novel Role for IL-15 in the Control of Renal Epithelial-Mesenchymal Transition: IL-15 Counteracts TGF-β 1-Induced EMT in Renal Fibrosis

International Journal of Cell Biology
Aurore DevocelleJulien Giron-Michel

Abstract

Renal tubulointerstitial fibrosis is the final common pathway in end-stage renal disease and is characterized by aberrant accumulation of extracellular matrix (ECM) components secreted by myofibroblasts. Tubular type 2 EMT, induced by TGF-β, plays an important role in renal fibrosis, by participating directly or indirectly in myofibroblasts generation. TGF-β1-induced apoptosis and fibrosis in experimental chronic murine kidney diseases are concomitantly associated with an intrarenal decreased expression of the IL-15 survival factor. Since IL-15 counteracts TGF-β1 effects in different cell models, we analyzed whether (1) human chronic inflammatory nephropathies evolving towards fibrosis could be also characterized by a weak intrarenal IL-15 expression and (2) IL-15 could inhibit epithelial-mesenchymal transition (EMT) and excess matrix deposition in human renal proximal tubular epithelial cells (RPTEC). Our data show that different human chronic kidney diseases are characterized by a strong decreased expression of intrarenal IL-15, which is particularly relevant in diabetic nephropathy, in which type 2 tubular EMT plays an important role in fibrosis. Moreover, primary epithelial tubular cultures deprived of growth supplements ra...Continue Reading

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Citations

Feb 6, 2020·Acta Cirúrgica Brasileira·Clóvis Ney Pinheiro MacêdoMarcio Wilker Soares Campelo
Apr 3, 2020·Future Medicinal Chemistry·Yue-Yu GuHui-Yao Lan
Oct 30, 2020·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Songling JiangHunjoo Ha
Dec 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yanwen MaoBing Guo

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Datasets Mentioned

BETA
GPL8300
U95
GPL14663

Methods Mentioned

BETA
biopsies
biopsy
fluorescence microscopy
flow cytometry
FCS
nuclear translocation

Software Mentioned

R
MAS
TRIBVN ICS Framework
FlowJo
Image J
GraphPad Prism

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