F2RL1 Inhibition Alleviates Lipotoxicity-Induced Kidney Injury Through the Hippo Pathway in Diabetic Kidney Disease

Diabetic kidney disease (DKD), which is emerging as a pervasive global health concern and a considerable economic burden, is characterized by a detrimental effect on renal function and structure. Recent research indicates that the progression of DKD is facilitated by lipotoxic injury to tubular epithelial cells (TECs). However, the specific mechanisms that contribute to this cellular damage have yet to be fully elucidated. Our results revealed a significant upregulation of F2RL1 in vivo and in vitro models, which was positively correlated with the expression of inflammatory factors. Knockdown of F2RL1 significantly reduced inflammatory response in palmitate-stimulated HK-2 cells. Mechanistically, F2RL1 might exacerbate lipotoxicity-induced DKD through the modulation of the Hippo signaling pathway. Collectively, these findings suggest that modulating F2RL1 expression may be a strategic approach to mitigate the inflammatory damage to RTECs associated with DKD, potentially through its involvement in the Hippo signaling pathway. Given these findings, F2RL1 merits consideration as a candidate therapeutic target for DKD.