Role of interleukin 17 in TGF-β signaling-mediated renal interstitial fibrosis

Abstract

BackgroundSeveral studies suggest IL-17 is involved in the pathogenesis of organ fibrosis. The exact role of IL-17 in renal interstitial fibrosis has not been fully elucidated. MethodsWe compared the histopathology of renal fibrosis as well as profibrotic TGF-β signaling in wild-type (WT) and IL-17 knock-out (IL-17−/−) mice using UUO as the disease model. To find out the possible mechanisms involved in the exacerbated renal fibrosis happened to IL-17−/− mice, we analyzed the pattern of ECM synthesis by different fibroblasts cultured with IL-17 and associated signaling mediators. ResultsOn day3 and day7, IL-17−/− mice developed more severe renal fibrosis compared with WT mice. IL-17 had an inhibitory factor in TGF-β-induced renal fibroblast activation and ECM synthesis, and sequentially in renal interstitial fibrosis, via down-regulation of Smad -independent pathway (p38MAPK and AKT phosphorylations). ConclusionIL-17 acts an inhibitory factor in TGF-β-induced renal fibroblast activation and ECM synthesis, and sequentially in renal interstitial fibrosis, via down-regulation of Smad-independent pathway (p38MAPK and AKT phosphorylations). Clarifying the novel regulatory mechanisms of fibrosis by the cytokine IL-17 may lead to a new therapeutic approach for progressive renal disease and fibrosis.