Hepatic stellate cell-specific knockout of transcriptional intermediary factor 1 gamma aggravates liver fibrosis
- Authors
- Lee, Eun Ju; Hwang, Injoo; Lee, Ji Yeon; Park, Jong Nam; Kim, Keun Cheon; Kim, Irene; Moon, Dodam; Park, Hyomin; Lee, Seo-Yeon; Kim, Hong Sug; Jun, Dae Won; Park, Sung-Hye; Kim, Hyo-Soo
- Issue Date
- Jun-2020
- Publisher
- ROCKEFELLER UNIV PRESS
- Citation
- JOURNAL OF EXPERIMENTAL MEDICINE, v.217, no.6, pp.1 - 22
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Volume
- 217
- Number
- 6
- Start Page
- 1
- End Page
- 22
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/9786
- DOI
- 10.1084/jem.20190402
- ISSN
- 0022-1007
- 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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