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  3. The mechanical mechanism of angiotensin II induced activation of hepatic stellate cells promoting portal hypertension

The mechanical mechanism of angiotensin II induced activation of hepatic stellate cells promoting portal hypertension

  • Eur J Cell Biol. 2024 Jun;103(2):151427. doi: 10.1016/j.ejcb.2024.151427.
Yiheng Zhang 1,  Mulan Xing 1,  Fansheng Meng 1,  Ling Zhu 2,  Qingchuan Huang 1,  Tianle Ma 1,  Huihua Fang 3,  Xujing Gu 1,  Suzhou Huang 1,  Xinyu Wu 1,  Gaohong Lv 1,  Jun Guo 2,  Li Wu 4,  Xin Liu 5,  Zhipeng Chen 6
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 2 State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 3 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210004, China.
  • 4 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: wuli@njucm.edu.cn.
  • 5 Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, China. Electronic address: arron_liu@163.com.
  • 6 Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: czpcpu2000@hotmail.com.
PMID: 38820882 DOI: 10.1016/j.ejcb.2024.151427
Abstract

In the development of chronic liver disease, the hepatic stellate cell (HSC) plays a pivotal role in increasing intrahepatic vascular resistance (IHVR) and inducing portal hypertension (PH) in cirrhosis. Our research demonstrated that HSC contraction, prompted by angiotensin II (Ang II), significantly contributed to the elevation of type I collagen (COL1A1) expression. This increase was intimately associated with enhanced cell tension and YAP nuclear translocation, mediated through α-smooth muscle actin (α-SMA) expression, microfilaments (MF) polymerization, and stress fibers (SF) assembly. Further investigation revealed that the Rho/ROCK signaling pathway regulated MF polymerization and SF assembly by facilitating the phosphorylation of cofilin and MLC, while CA2+ chiefly governed SF assembly via MLC. Inhibiting α-SMA-MF-SF assembly changed Ang II-induced cell contraction, YAP nuclear translocation, and COL1A1 expression, findings corroborated in cirrhotic mice models. Overall, our study offers insights into mitigating IHVR and PH through cell mechanics, heralding potential breakthroughs.

Keywords

COL1A1; Hepatic stellate cell; Microfilaments; Portal hypertension; Stress fibers; α-SMA.

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