Hepatocyte-specific TAZ deletion downregulates p62/ Sqstm1 expression in nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is characterized by inflammation, hepatocellular injury, and different degrees of fibrosis. Previous studies have indicated that the transcriptional coactivator with PDZ-binding motif TAZ (WWTR1) is correlated with the increased level of liver cholesterol which suppresses TAZ proteasomal degradation and promotes fibrotic NASH by activating soluble adenylyl cyclase-calcium-RhoA pathway. However, the exact mechanism by which TAZ promotes inflammatory and hepatocyte injury has not yet been fully addressed. Reportedly, p62/Sqstm1plays a pivotal role in inflammatory and hepatocyte injury during NASH development. Here, we demonstrated that p62/Sqstm1 was overexpressed in the livers of mouse NASH models in a TAZ-dependent manner. In addition, hepatocyte-specific TAZ deletion reduced p62/Sqstm1 both in vitro and in vivo. Strikingly, luciferase reporter data demonstrated that p62/Sqstm1 is a TAZ/TEAD target gene and can be transcriptionally regulated by TAZ, indicating that hepatocyte-specific TAZ deletion downregulates p62/Sqstm1 expression in NASH. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

The study showed a dependency relationship between TAZ and p62/Sqstm1 in NASH, where TAZ can transcriptionally regulate p62/Sqstm1. This finding reveals the regulatory mechanism of TAZ in inflammation and hepatocyte injury.