Research Article Details
| Article ID: | A05190 |
| PMID: | 33341674 |
| Source: | Biochem Biophys Res Commun |
| Title: | Hepatocyte-specific TAZ deletion downregulates p62/ Sqstm1 expression in nonalcoholic steatohepatitis. |
| Abstract: | 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. |
| DOI: | 10.1016/j.bbrc.2020.12.038 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D055 | Calcium | Chemical drug | DB01373 | CAST; COMP; CP; BMP4; MGP | -- | Under clinical trials | Details |