Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro.
OBJECTIVE
To investigate the role of insulin-like growth factor binding protein-7 (IGFBP-7) in the activation and transdifferentiation of hepatic stellate cells (HSC) in vitro.


METHODS
Rat HSC-T6 cells were cultured in separate dishes and treated with various concentration of transforming growth factor (TGF)-beta(1), IGFBP-7 or anti-IGFBP-7 antibody for 24 h. The supernatant or a cytoplasm suspension was obtained from cultured HSC, followed by transfer of cells to form cell-coated dishes. Immunocytochemistry and Western blotting were used to analyze the expression of IGFBP-7 induced by TGF-beta(1) and the level of fibronectin, collagen I and alpha-smooth muscle actin (SMA). The pro-apoptotic effect of anti-IGFBP-7 antibody was determined by flow cytometry.


RESULTS
Immunocytochemistry and Western blotting revealed that the expression of IGFBP-7 in TGF-beta(1) treated HSC was significantly up-regulated compared to that in the control group. In addition, fibronectin, collagen I and alpha-SMA also showed enhanced expression in accordance with the transdifferentiation process in a dose-dependent manner to some extent. Moreover, flow cytometry suggested that anti-IGFBP-7 antibody induced apoptosis of activated HSC, which is responsible for the development of liver fibrosis, and may represent a novel pathway and target for therapeutic intervention.


CONCLUSIONS
IGFBP-7 showed increased expression in activated HSC and played an important role in the activation and transdifferentiation process of HSC. Anti-IGFBP-7 antibody may ameliorate liver fibrogenesis.
Liu
Li-Xin
LX
Institute of Liver Disease of Shanxi Medical University, Mailbox 206, 56 Xinjian South Road, Taiyuan 030001, Shanxi Province, China. lixinl6@yahoo.com
Huang
Shuai
S
Zhang
Qian-Qian
QQ
Liu
Yi
Y
Zhang
Dong-Mei
DM
Guo
Xiao-Hong
XH
Han
De-Wu
DW
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000494:pharmacology*; D010641:Phenotype; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D024042:Collagen Type I; D005353:Fibronectins; D018969:Insulin-Like Growth Factor Binding Proteins; D016212:Transforming Growth Factor beta; C102529:insulin-like growth factor binding protein-related protein 1