Papers of The 4th Japan Scar Workshop

8. Treatment strategy for liver fibrosis by targeting the TGF-β/Smad signal

Yutaka Inagaki1, Sachie Nakao1, Tadashi Moro1,2, Kenichiro Mikami1,
Reiichi Higashiyama1
1:Research Unit for Tissue Remodeling and Regeneration, School of Medicine and the Institutes of Medical Sciences, Tokai University, Isehara, Japan
2:Research Laboratory, Minophagen Pharmaceutical Co. Ltd., Zama, Japan

Collagen content in tissues is under the control of a dynamic balance between its production and degradation, and a disruption of this equilibrium results in either organ fibrosis or impaired tissue integrity. Irrespective of the etiologies of hepatic injury, liver fibrosis is caused commonly by a chronic and uncontrolled inflammatory/repair process leading to excessive deposition of collagen and other components of extracellular matrix in the liver. Hepatic stellate cells (HSC) are the main producers of type I collagen in fibrotic liver, and transforming growth factor- (TGF-) and its intracellular mediators Smad proteins play key roles in stimulating type I collagen gene transcription in HSC. Thus, a number of studies have focused on the suppression of the TGF-/Smad signal to treat liver fibrosis. Nuclear accumulation of phosphorylated Smad3 is considered to be a hallmark of activated HSC, and our recent study has identified galectin-7 as one of the Smad3-interacting factors that accelerate nuclear export of Smad3 and suppress collagen gene transcription in response to HGF treatment.
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