GSPE alleviates renal fibrosis by inhibiting the activation of C3/ HMGB1/ TGF-β1 pathway

In this study, we aimed to identify the effect of GSPE on C3 in the chronic kidney fibrosis and evaluate the possible mechanism. We observed that administration of GSPE relieves inflammation and chronic renal fibrosis in mouse models of UUO. GSPE inhibited C3 secreted by macrophages to relieve renal interstitial inflammation. In vitro, we found that C3 stimulated HMGB1 translocation form nucleus to cytoplasm and promote the expression of pro-inflammatory cytokines including TGF-β1 in primary renal tubular epithelial cells (PTEC), which could be inhibited by GSPE. Meanwhile, GSPE could also decreased HMGB1-induced EMT of PTEC through suppresses the HMGB1/TLR4/p65/TGF-β pathway. In addition, the myofibroblast activation was inhibited by GSPE via TGF-β1/Smad2/3 signaling pathways in normal rat kidney fibroblast (NRK-49F) cells. Overall, these observations provide that GSPE alleviates renal fibrosis by inhibiting the C3/HMGB1/TGF-β1 pathway and could thus lead to find the potential therapy for the suppression of renal fibrosis.Graphical abstract
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research