|
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. |
