Gα12 overexpression induced by miR-16 dysregulation contributes to liver fibrosis by promoting autophagy in hepatic stellate cells

Journal of Hepatology
Kyu Min KimSang Geon Kim

Abstract

Hepatic stellate cells (HSCs) have a role in liver fibrosis. Guanine nucleotide-binding α-subunit 12 (Gα12) converges signals from G-protein-coupled receptors whose ligand levels are elevated in the environment during liver fibrosis; however, information is lacking on the effect of Gα12 on HSC trans-differentiation. This study investigated the expression of Gα12 in HSCs and the molecular basis of the effects of its expression on liver fibrosis. Gα12 expression was assessed by immunostaining, and immunoblot analyses of mouse fibrotic liver tissues and primary HSCs. The role of Gα12 in liver fibrosis was estimated using a toxicant injury mouse model with Gα12 gene knockout and/or HSC-specific Gα12 delivery using lentiviral vectors, in addition to primary HSCs and LX-2 cells using microRNA (miR) inhibitors, overexpression vectors, or adenoviruses. miR-16, Gα12, and LC3 were also examined in samples from patients with fibrosis. Gα12 was overexpressed in activated HSCs and fibrotic liver, and was colocalised with desmin. In a carbon tetrachloride-induced fibrosis mouse model, Gα12 ablation prevented increases in fibrosis and liver injury. This effect was attenuated by HSC-specific lentiviral delivery of Gα12. Moreover, Gα12 activati...Continue Reading

Citations

Oct 10, 2018·The Journal of Clinical Investigation·Tae Hyun KimSang Geon Kim
Mar 27, 2019·Antioxidants & Redox Signaling·Ji Hye YangSung Hwan Ki
Jun 18, 2019·BioMed Research International·Yinghao Yu, Jijun Zhao
Jun 25, 2020·Experimental & Molecular Medicine·Yoon Mee YangSang Geon Kim
Dec 14, 2018·International Journal of Molecular Sciences·Paola DongiovanniAnna Ludovica Fracanzani
Sep 26, 2019·Frontiers in Cell and Developmental Biology·Konstantinos KounakisNektarios Tavernarakis
Sep 22, 2020·Clinical and Molecular Hepatology·Yun Seok Kim, Sang Geon Kim
Jan 4, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Lei HouLiying Li
Dec 30, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Seung Jung KimSung Hwan Ki
Feb 10, 2021·Cell Chemical Biology·Masayasu ToyomotoMasatoshi Hagiwara
Feb 16, 2021·World Journal of Hepatology·Elias KouroumalisDimitrios N Samonakis
Feb 4, 2019·Journal of Hepatology·Manon AllaireSophie Lotersztajn
Apr 29, 2021·Antioxidants & Redox Signaling·Xiaocheng Charlie DongHyeong Geug Kim
Jun 25, 2021·Archives of Pharmacal Research·Seonghwan Hwang, Yoon Mee Yang
Jun 15, 2021·Molecular Aspects of Medicine·Hui QianWen-Xing Ding
Aug 25, 2021·International Immunopharmacology·Fangming YangZhun Xiao
Dec 11, 2021·Cellular and Molecular Gastroenterology and Hepatology·Chung Hwan HongEun Hee Koh

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