Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 535, Issue -, Pages 60-65Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.12.038
Keywords
Nonalcoholic steatohepatitis; TAZ /WINTR1; p62 /SQSTM1
Categories
Funding
- CAS Light of West China Program [XAB2018AW09]
- Natural Science Foundation of Ningxia [2018AAC03078]
- Scientific Research Project of Higher Education of Ningxia [NGY2018-97]
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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.
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.
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