1. Academic Validation
  2. The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition

The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition

  • Theranostics. 2019 Oct 12;9(25):7566-7582. doi: 10.7150/thno.36942.
Kun Zhang 1 Mengxia Zhang 1 Qingbin Yao 1 Xiaohui Han 1 Yanmian Zhao 1 Lina Zheng 1 Guantong Li 2 Qi Liu 1 Yanan Chang 3 Peijun Zhang 4 Hongmei Cui 1 Zhemin Shi 1 Ting Chen 1 Zhi Yao 5 Tao Han 2 Wei Hong 1
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, Key Laboratory of Immune Microenvironment and Disease of Ministry of Education, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • 2 The Third Central Clinical College of Tianjin Medical University, Department of Hepatology and Gastroenterology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cells, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, China.
  • 3 Department of Pathology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
  • 4 Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China.
  • 5 Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of Ministry of Education, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Abstract

Liver fibrosis leading to cirrhosis is one of the major health burdens worldwide with currently limited therapeutic options available. Long noncoding RNAs (lncRNAs) play important roles in various biological and pathological processes in a cell- or tissue-specific manner. However, there is still an important gap in the understanding of the role of hepatocyte-specific lncRNAs in liver fibrosis. Methods: The expressions of lnc-Hser in human and mice fibrotic livers as well as primary hepatocytes (HCs) of mice developing liver fibrosis were determined by real-time RT-PCR. The roles and mechanisms of lnc-Hser in HCs and liver fibrosis were determined in vitro and in vivo. Results: In this study, we have identified a hepatocyte-specifically expressed lnc-Hser, which was reduced in human and mice fibrotic livers as well as primary HCs of mice developing liver fibrosis. We have shown that silencing lnc-Hser aggravated liver fibrosis both in vitro and in vivo through inducing the epithelial-mesenchymal transition (EMT) and the Apoptosis of HCs. In addition, knockdown of lnc-Hser promoted hepatic stellate cells (HSCs) activation through the signals derived from injured HCs. Mechanistically, we have revealed that lnc-Hser inhibited HCs Apoptosis via the C5AR1-Hippo-YAP pathway and suppressed HCs EMT via the Notch signaling. Conclusions: Our work has identified a hepatocyte-specific lnc-HSER that regulates liver fibrosis, providing a proof that this molecule is a novel biomarker for damaged HCs and a potential target for anti-fibrotic therapy.

Keywords

C5AR1; Notch; hepatocyte; liver fibrosis; lncRNA.

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