Loading...
Please wait, while we are loading the content...
Similar Documents
IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?
| Content Provider | MDPI |
|---|---|
| Author | François, Hélène Devocelle, Aurore Lecru, Lola Ferlicot, Sophie Bessede, Thomas Candelier, Jean-Jacques Giron-Michel, Julien |
| Copyright Year | 2021 |
| Description | Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. Recently, interleukin-15 (IL-15) has been implicated in fibrosis protection in several organs, with little evidence in the kidney. Since endogenous IL-15 expression decreased in nephrectomized human allografts evolving toward fibrosis and kidneys in the unilateral ureteral obstruction (UUO) model, we explored IL-15’s renoprotective role by pharmologically delivering IL-15 coupled or not with its soluble receptor IL-15Rα. Despite the lack of effects on myofibroblast accumulation, both IL-15 treatments prevented tubulointerstitial fibrosis (TIF) in UUO as characterized by reduced collagen and fibronectin deposition. Moreover, IL-15 treatments inhibited collagen and fibronectin secretion by transforming growth factor-β (TGF-β)-treated primary myofibroblast cultures, demonstrating that the antifibrotic effect of IL-15 in UUO acts, in part, through a direct inhibition of ECM synthesis by myofibroblasts. In addition, IL-15 treatments resulted in decreased expression of monocyte chemoattractant protein 1 (MCP-1) and subsequent macrophage infiltration in UUO. Taken together, our study highlights a major role of IL-15 on myofibroblasts and macrophages, two main effector cells in renal fibrosis, demonstrating that IL-15 may represent a new therapeutic option for CKD. |
| Starting Page | 11698 |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms222111698 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 21 |
| Volume Number | 22 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-10-28 |
| Access Restriction | Open |
| Subject Keyword | International Journal of Molecular Sciences Urology and Nephrology Chronic Kidney Disease Fibrosis Unilateral Ureteral Obstruction Interleukin-15 Myofibroblasts Extracellular Matrix |
| Content Type | Text |
| Resource Type | Article |
