Hepatic Stellate Cell-specific Knockout of Transcriptional Intermediary Factor 1γ Aggravates Liver Fibrosis

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2020 Apr 9

PMID 32267915

Citations 10

Authors

Eun Ju Lee

Injoo Hwang

Ji Yeon Lee

Jong Nam Park

Keun Cheon Kim

Irene Kim

Dodam Moon

Hyomin Park

Seo-Yeon Lee

Hong Sug Kim

Dae Won Jun

Sung-Hye Park

Hyo-Soo Kim

Affiliations

Soon will be listed here.

Abstract

Transforming growth factor β (TGFβ) is a crucial factor in fibrosis, and transcriptional intermediary factor 1γ (TIF1γ) is a negative regulator of the TGFβ pathway; however, its role in liver fibrosis is unknown. In this study, mesenchymal stem cells derived from human embryonic stem cells (hE-MSCs) that secrete hepatocyte growth factor (HGF) were used to observe the repair of thioacetamide (TAA)-induced liver fibrosis. Our results showed that TIF1γ was significantly decreased in LX2 cells when exposed to TGFβ1. Such decrease of TIF1γ was significantly prevented by co-culture with hE-MSCs. Interaction of TIF1γ with SMAD2/3 and binding to the promoter of the α-smooth muscle gene (αSMA) suppressed αSMA expression. Phosphorylation of cAMP response element-binding protein (CREB) and binding on the TIF1γ promoter region induced TIF1γ expression. Furthermore, hepatic stellate cell-specific TIF1γ-knockout mice showed aggravation of liver fibrosis. In conclusion, loss of TIF1γ aggravates fibrosis, suggesting that a strategy to maintain TIF1γ during liver injury would be a promising therapeutic approach to prevent or reverse liver fibrosis.

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