Maoyao Wen1, Ruoting Men2, Xiaojing Liu3, Li Yang4. 1. Division of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China. 2. Division of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China; Stanley Ho Center for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, China; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, China. 3. Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address: liuxq@scu.edu.cn. 4. Division of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: yangli_hx@scu.edu.cn.
Abstract
AIMS: This study aimed to determine the role of miR-30c in the process of hepatic stellate cells (HSCs) activation and liver fibrosis/cirrhosis and to explore the underlying mechanism. MAIN METHODS: A microarray analysis of miRNAs in HSCs was performed, and quantitative RT-PCR analyses were conducted to validate the results in HSCs, cirrhotic liver tissues and plasma. Rat HSCs were stimulated with angiotensin II (AngII) and transfected with miR-30c mimics/inhibitor to elucidate the underlying mechanism. KEY FINDINGS: miR-30c was down-regulated during HSCs activation and in cirrhotic liver tissues and plasma. This miRNA was found to be involved in HSCs activation by repressing the expression of one of its target genes-plasminogen activator inhibitor-1 (PAI-1), and AngII stimulation decreased the expression of miR-30c. However, the up-regulation of miR-30c by specific mimics could down-regulate the mRNA and protein expression of α-SMA, a marker of HSCs activation, in AngII-stimulated HSCs and attenuate the AngII-induced activation of HSCs. SIGNIFICANCE: miR-30c is involved in HSCs activation and might be a novel biomarker of liver fibrosis/cirrhosis.
AIMS: This study aimed to determine the role of miR-30c in the process of hepatic stellate cells (HSCs) activation and liver fibrosis/cirrhosis and to explore the underlying mechanism. MAIN METHODS: A microarray analysis of miRNAs in HSCs was performed, and quantitative RT-PCR analyses were conducted to validate the results in HSCs, cirrhotic liver tissues and plasma. Rat HSCs were stimulated with angiotensin II (AngII) and transfected with miR-30c mimics/inhibitor to elucidate the underlying mechanism. KEY FINDINGS:miR-30c was down-regulated during HSCs activation and in cirrhotic liver tissues and plasma. This miRNA was found to be involved in HSCs activation by repressing the expression of one of its target genes-plasminogen activator inhibitor-1 (PAI-1), and AngII stimulation decreased the expression of miR-30c. However, the up-regulation of miR-30c by specific mimics could down-regulate the mRNA and protein expression of α-SMA, a marker of HSCs activation, in AngII-stimulated HSCs and attenuate the AngII-induced activation of HSCs. SIGNIFICANCE: miR-30c is involved in HSCs activation and might be a novel biomarker of liver fibrosis/cirrhosis.
Authors: Lawrence N Barrera; P Matthew Ridley; Camino Bermejo-Rodriguez; Eithne Costello; Pedro A Perez-Mancera Journal: J Physiol Biochem Date: 2022-06-29 Impact factor: 4.158