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Published on: April 24, 2021
CHOP aggravates hepatocyte apoptosis upon endoplasmic reticulum stress by downregulating autophagy
Jia-Yu Wu1, Bing Han1, Ting Yang1
1Department of Pathophysiology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou Province, China; Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou Province, China.
Abstract:
Endoplasmic reticulum (ER) stress-induced apoptosis plays a crucial role in various liver diseases. Hepatocytes respond to ER stress by activating the unfolded protein response and autophagy, which is essential for maintaining ER homeostasis. However, failure to restore ER balance via autophagy contributes to apoptosis. In this study, we aimed to explore the role of C/EBP homologous protein (CHOP) in regulating ER stress-induced apoptosis in rat hepatocytes. We found that CHOP downregulates autophagy, aggravating apoptosis. Our results revealed that inhibition of CHOP expression enhanced autophagy and reduced DTT-induced apoptosis in BRL-3A cells, whereas CHOP overexpression worsened apoptosis. Chromatin immunoprecipitation assays revealed that CHOP negatively regulates autophagy-related genes, such as ATG12, ATG5, and LC3. These findings suggest that CHOP modulation plays a crucial role in ER stress-induced hepatocyte apoptosis by regulating autophagy.
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