C/EBP- induces autophagy by binding to Beclin1 through its own acetylation modification in activated hepatic stellate cells
Experimental Cell Research(2021)
Abstract
The activation of hepatic stellate cells (HSCs) plays a key role in the occurrence of liver fibrosis,and 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 alpha (C/EBP-alpha) 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-alpha 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-alpha 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-alpha. Here we show that C/EBP-alpha promotes the occurrence of autophagy in HSCs and the autophagy induced by C/EBP-alpha belongs to mitophagy. The stability of C/EBP-alpha protein regulates the level of autophagy in HSCs. In addition, acetylation of C/EBP-alpha also regulates the occurrence of autophagy in HSCs. Acetylation of lysine at positions K298, K302 and K326 of C/EBP-alpha promotes its binding to Beclin1. In conclusion, our study uncovers the role of C/EBP-alpha in regulating autophagy in HSCs, thereby providing a new strategy for clinical treatment of liver fibrosis.
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Key words
C/EBP-alpha,Autophagy,Beclin1,Acetylation,Hepatic stellate cells
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