CD47, a novel YAP target gene, contributes to hepatic stellate cell activation and liver fibrosis induced by high-fat diet
Ya Li,
Lin Dong,
Xuecui Yin,
Xiaohan Wang,
Xiaohui Zhu,
Pengyuan Zheng,
Youcai Tang
Affiliations
Ya Li
Department of Pediatrics, Henan Key Laboratory of Rehabilitation Medicine, Henan Joint International Research Laboratory of Chronic Liver Injury and Outstanding Foreign Scientists Studio for Chronic Liver Injury, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Lin Dong
Department of Pediatrics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Xuecui Yin
Department of Internal Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Xiaohan Wang
Department of Pediatrics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Xiaohui Zhu
Department of Pediatrics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Pengyuan Zheng
Henan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall B. J. Medical Research Center of Zhengzhou University, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Corresponding author.
Youcai Tang
Department of Pediatrics, Henan Key Laboratory of Rehabilitation Medicine, Henan Joint International Research Laboratory of Chronic Liver Injury and Outstanding Foreign Scientists Studio for Chronic Liver Injury, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Corresponding author.
Activated hepatic stellate cells (HSCs) have been widely recognized as a primary source of pathological myofibroblasts, leading to the accumulation of extracellular matrix and liver fibrosis. CD47, a transmembrane glycoprotein expressed on the surface of various cell types, has been implicated in non-alcoholic fatty liver disease. However, the precise role of CD47 in HSC activation and the underlying regulatory mechanisms governing CD47 expression remain poorly understood. In this study, we employed single-cell RNA sequencing analysis to investigate CD47 expression in HSCs from mice subjected to a high-fat diet. CD47 silencing in HSCs markedly inhibited the expression of fibrotic genes and promoted apoptosis. Mechanistically, we found that Yes-associated protein (YAP) collaborates with TEAD4 to augment the transcriptional activation of CD47 by binding to its promoter region. Notably, disruption of the interaction between YAP and TEAD4 caused a substantial decrease in CD47 expression in HSCs and reduced the development of high-fat diet-induced liver fibrosis. Our findings highlight CD47 as a critical transcriptional target of YAP in promoting HSC activation in response to a high-fat diet. Targeting the YAP/TEAD4/CD47 signaling axis may hold promise as a therapeutic strategy for liver fibrosis.
