(A) role of the Hippo pathway in renal tubulointerstitial fibrosis eevelopment

Abstract

Renal tubulointerstitial fibrosis (TIF) is the final step of various renal injuries leading to chronic kidney disease. The mammalian Hippo-Salvador signaling pathway has been implicated in the control of cell proliferation, cell death, tissue regeneration, and tumorigenesis. However, the role of the mammalian Hippo pathway in TIF development has not been investigated. Here, I report that the Hippo-Salvador pathway plays a role in TIF development. An in vitro study using renal tubular cells, HK-2 cells, showed that SAV1 deficiency led to the increase of activity of YAP/TAZ, which induced the expression of $TGF-\beta 2$ and $TGF-\beta$ receptor II. Furthermore, SAV1 deficiency led to an induction of pro-fibrotic or EMT marker genes, mediating the increase of YAP/TAZ activity. Collectively, these results suggest that the Hippo pathway plays a role in the pathogenesis of TIF, and targeting this pathway may be a therapeutic strategy for reducing TIF.