Atorvastatin reduces renal interstitial fibrosis caused by unilateral ureteral obstruction through inhibiting the transcriptional activity of YAP

Abstract

Renal interstitial fibrosis is the primary pathological basis for the progression and development of various chronic kidney diseases, ultimately leading to renal failure. Obstructive kidney disease caused by conditions such as kidney stones, is a common cause of renal fibrosis. The Hippo pathway is a crucial signaling pathway that senses mechanical forces and is involved in the pathophysiology of fibrosis. In this study, we established a mouse model of obstructive kidney disease induced by unilateral ureteral obstruction (UUO). The UUO procedure significantly upregulated YAP and fibrosis-related gene expression in a time-dependent manner. Morphologically, the renal fibrotic lesions associated with hydronephrosis progressively worsened over time in the UUO group. Atorvastatin, which is widely used to lower blood cholesterol levels, has recently been shown to inhibit Yes1 associated protein (YAP). We treated UUO mice with atorvastatin for 3 and 10 days and observed a decrease in the expression of YAP and fibrosis-related genes at the mRNA and protein levels, along with a reduction in the renal fibrosis analyzed by Masson's staining. These findings suggest that atorvastatin may serve as a preventive agent for fibrosis associated with obstructive kidney disease.

Keywords: Atorvastatin; Renal interstitial fibrosis; The Hippo pathway; Ullilateral ureteral obstruction; Yes-associated protein.