Targeting FAM3D improves renal fibrosis via inhibiting tubular cell inflammation and pyroptosis

Renal fibrosis is the common pathological feature of CKD and plays a key role in the progression of CKD to ESRD. However, the underlying mechanisms of renal fibrosis initiation and progression remains unclear. FAM3D belongs to FAM3 gene family and is associate with nutrient regulation and inflammation. In this study, we found that FAM3D was de novo expressed in tubules during CKD and positively correlated with fibrogenesis. Knockout of tubular FAM3D effectively improved UIRI- or UUO-induced renal fibrosis. Mechanistically, FAM3D depletion suppressed NF-κB activation in epithelial cells via FPRs/MAPK pathway and then alleviated cell pyroptosis. Furthermore, blockade of FPR1/2 prevented renal inflammation, tubular cell pyroptosis, and fibrosis development. Our findings provided the first evidence for the critical role of FAM3D in renal fibrosis progression.