Fibroblast growth factor 18 attenuates renal fibrosis via AMPK/NOX4 pathway in mice.

Renal fibrosis, particularly tubulointerstitial fibrosis, is a prevalent pathological process contributing to the progression of chronic kidney disease (CKD). A growing body of evidence indicates that fibroblast growth factors (FGFs) play critical roles in kidney pathophysiology. However, the role of FGF18 in the pathogenesis of kidney fibrosis and the underlying mechanisms remain unclear. In this study, we discovered a significant upregulation of FGF18 in a folic acid (FA)-induced renal fibrosis model, as well as in transforming growth factor β (TGF-β) stimulated human proximal tubular cells (HK-2 cells). Furthermore, overexpression of FGF18 in the kidney significantly alleviated FA-induced fibrosis and diminished oxidative stress. Mechanistically, FGF18 upregulated AMP-activated protein kinase (AMPK) phosphorylation via its receptor FGFR3, leading to decreased NOX4-ROS levels, reduced oxidative stress, and ultimately inhibited the expression of fibrosis-related proteins. In conclusion, our findings suggest that FGF18 attenuates FA-induced renal fibrosis, at least in partly via AMPK/NOX4 pathway.