Inhibition of TGF-β1 Signaling by IL-15: A Novel Role for IL-15 in the Control of Renal Epithelial-Mesenchymal Transition: IL-15 Counteracts TGF-β1-Induced EMT in Renal Fibrosis
Joint Authors
Azzarone, Bruno
Desterke, Christophe
Devocelle, Aurore
Lecru, Lola
François, Hélène
Gallerne, Cindy
Eid, Pierre
Estelle, Oberlin
Giron-Michel, Julien
Source
International Journal of Cell Biology
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-07-07
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
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 rapidly produce active TGF-β1 inducing a “spontaneous” EMT process characterized by the loss of membrane-bound IL-15 (mbIL-15) expression.
Both “spontaneous” EMT and recombinant human (rh) TGF-β1-induced EMT models can be inhibited by treating RPTEC and HK2 cells with rhIL-15.
Through a long-lasting phospho-c-jun activation, IL-15 inhibits rhTGF-β1-induced Snail1 expression, the master inducer of EMT, and blocks TGF-β1-induced tubular EMT and downstream collagen synthesis.
In conclusion, our data suggest that intrarenal IL-15 could be a natural inhibitor of TGF-β in human kidney able to guarantee epithelial homeostasis and to prevent EMT process.
Thus, both in vivo and in vitro an unbalance in intrarenal IL-15 and TGF-β1 levels could render RPTEC cells more prone to undergo EMT process.
Exogenous IL-15 treatment could be beneficial in some human nephropathies such as diabetic nephropathy.
American Psychological Association (APA)
Devocelle, Aurore& Lecru, Lola& François, Hélène& Desterke, Christophe& Gallerne, Cindy& Eid, Pierre…[et al.]. 2019. Inhibition of TGF-β1 Signaling by IL-15: A Novel Role for IL-15 in the Control of Renal Epithelial-Mesenchymal Transition: IL-15 Counteracts TGF-β1-Induced EMT in Renal Fibrosis. International Journal of Cell Biology،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1158541
Modern Language Association (MLA)
Devocelle, Aurore…[et al.]. Inhibition of TGF-β1 Signaling by IL-15: A Novel Role for IL-15 in the Control of Renal Epithelial-Mesenchymal Transition: IL-15 Counteracts TGF-β1-Induced EMT in Renal Fibrosis. International Journal of Cell Biology No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1158541
American Medical Association (AMA)
Devocelle, Aurore& Lecru, Lola& François, Hélène& Desterke, Christophe& Gallerne, Cindy& Eid, Pierre…[et al.]. Inhibition of TGF-β1 Signaling by IL-15: A Novel Role for IL-15 in the Control of Renal Epithelial-Mesenchymal Transition: IL-15 Counteracts TGF-β1-Induced EMT in Renal Fibrosis. International Journal of Cell Biology. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1158541
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1158541