C/EBP-α induces autophagy by binding to Beclin1 through its own acetylation modification in activated hepatic stellate cells.
Exp Cell Res
; 405(2): 112721, 2021 08 15.
Article
in En
| MEDLINE
| ID: mdl-34217716
ABSTRACT
The activation of hepatic stellate cells (HSCs) plays a key role in the occurrence of liver fibrosisï¼and promoting the apoptosis of activated HSCs or reducing the number of activated HSCs can reverse the development of liver fibrosis. In our previous studies, we have demonstrated that the CCAAT/enhancer binding protein α (C/EBP-α) played an important role in promoting the apoptosis of activated HSCs, thereby exerting an anti-liver fibrosis effect. Unlike apoptosis, autophagy, as a caspase-independent programmed cell death, can promptly remove the abnormal accumulation of substances or damaged organelles in cells and play a key role in regulating the homeostasis of intracellular environment. However, it is still unclear whether C/EBP-α participates in the occurrence of autophagy in HSCs. Therefore, in this study, we firstly used the methods of Western blot and immunofluorescence to characterize the consequence of C/EBP-α overexpression on the expression of proteins LC3B, P62, ATG5 and Beclin1 which were related to autophagy in HSCs. Subsequently, we performed Western blot and site-directed mutagenesis methods to clarify the type and related mechanism of autophagy which was induced by C/EBP-α. Here we show that C/EBP-α promotes the occurrence of autophagy in HSCs and the autophagy induced by C/EBP-α belongs to mitophagy. The stability of C/EBP-α protein regulates the level of autophagy in HSCs. In addition, acetylation of C/EBP-α also regulates the occurrence of autophagy in HSCs. Acetylation of lysine at positions K298, K302 and K326 of C/EBP-α promotes its binding to Beclin1. In conclusion, our study uncovers the role of C/EBP-α in regulating autophagy in HSCs, thereby providing a new strategy for clinical treatment of liver fibrosis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
CCAAT-Enhancer-Binding Protein-alpha
/
Hepatic Stellate Cells
/
Beclin-1
Limits:
Animals
Language:
En
Journal:
Exp Cell Res
Year:
2021
Type:
Article