2. Academic Validation
  3. Inhibition of Notch1 signaling reduces hepatocyte injury in nonalcoholic fatty liver disease via autophagy

Inhibition of Notch1 signaling reduces hepatocyte injury in nonalcoholic fatty liver disease via autophagy

  • Biochem Biophys Res Commun. 2021 Apr 2;547:131-138. doi: 10.1016/j.bbrc.2021.02.039.
Min Zhang 1,  Pengbo Wu 2,  Ming Li 3,  Yitian Guo 4,  Tian Tian 5,  Xingchen Liao 6,  Shiyun Tan 7
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Key Laboratory of Hubei Province for Digestive Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address: LMmimier0823@163.com.
  • 2 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Key Laboratory of Hubei Province for Digestive Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address: wupengbo@whu.edu.cn.
  • 3 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Key Laboratory of Hubei Province for Digestive Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address: liming870221@sina.com.
  • 4 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Key Laboratory of Hubei Province for Digestive Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address: 695473128@qq.com.
  • 5 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Key Laboratory of Hubei Province for Digestive Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address: 1042408950@qq.com.
  • 6 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Key Laboratory of Hubei Province for Digestive Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address: 332997914@qq.com.
  • 7 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Key Laboratory of Hubei Province for Digestive Disease, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address: 812328105@qq.com.
PMID: 33610041 DOI: 10.1016/j.bbrc.2021.02.039
Abstract

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and an urgent target for clinical intervention. Notch1 signaling pathway activity was found to be related to the severity of NAFLD, but the specific mechanism is not precise. Here, we investigated the potential mechanisms of Notch1 signaling in the development of NAFLD. Firstly, we found that Notch1 signaling is activated in free fatty acids-treated HepG2 cells accompanied by lipid accumulation, Apoptosis, oxidative stress, and mitochondrial damage, which could be alleviated by Notch1 inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). In the meantime, we found that administration of DAPT activated the Autophagy pathway in NAFLD. Furthermore, the use of Autophagy Inhibitor chloroquine reversed the DAPT-mediated protective effect in NAFLD. All our results uncover a vital role of Notch1 in hepatocyte injury and metabolism of NAFLD, giving rise to a new sight for NAFLD treatment by regulation of Notch signaling and Autophagy pathway.

Keywords

Apoptosis; Autophagy; NAFLD; Notch1.

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