한빛사 논문
Eun Ju Lee1,*, Injoo Hwang2,*, Ji Yeon Lee2, Jong Nam Park2, Keun Cheon Kim2, Irene Kim2, Dodam Moon2, Hyomin Park2, Seo-Yeon Lee1,3, Hong Sug Kim4, Dae Won Jun5, Sung-Hye Park6, and Hyo-Soo Kim2,7,#
1Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
2Molecular Medicine & Biopharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
3Korean Medical Science Research Center for Healthy-Aging, Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University,Yangsan, Republic of Korea.
4Division of Genome Application, Macrogen, Inc., Seoul, Republic of Korea.
5Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Republic of Korea.
6Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
7Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
*E.J. Lee and I. Hwang contributed equally to this paper.
#Corresponding author
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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