Abstract
Renal fibrosis is an inevitable course of all kinds of progressive chronic kidney disease (CKD). Itaconic acid is an endogenous metabolite that has shown anti-inflammatory and antioxidant effects. 4-octyl itaconate (OI), a derivative of itaconic acid with higher fat solubility, can penetrate the cell membranes and be metabolized into itaconic acid in vitro. However, whether OI has an anti-renal fibrotic effect is still unclear. The current study purposed to investigate the anti-fibrotic effect in renal and the underlying mechanisms of OI. The unilateral ureteral occlusion (UUO) model and adenine-induced fibrosis model in Sprague-Dawley (SD) rats and Transforming growth factor-β1 (TGF-β1) induced HK-2 cells were applied to investigate the renoprotective effects of OI. This study reports for the first time that OI ameliorated renal fibrosis by suppressing the activation of TGF-β/Smad and nuclear factor kappa B (NF-κB) pathways, reducing generation of reactive oxygen species and inhibiting autophagy. These results clearly suggest that OI has great clinical potential for managing renal fibrosis.