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World J Gastroenterol. Feb 28, 2006; 12(8): 1303-1307
Published online Feb 28, 2006. doi: 10.3748/wjg.v12.i8.1303
Arg-gly-asp-mannose-6-phosphate inhibits activation and proliferation of hepatic stellate cells in vitro
Lian-Sheng Wang, Ying-Wei Chen, Ding-Guo Li, Han-Ming Lu
Lian-Sheng Wang, Ying-Wei Chen, Ding-Guo Li, Han-Ming Lu, Digestive Disease Laboratory, Xinhua Hospital, Shanghai Second Medical University, Shanghai 200092, China
Author contributions: All authors contributed equally to the work.
Supported by National Natural Science Foundation of China, No. 30170412
Correspondence to: Dr. Ding-Guo Li, Digestive Disease Laboratory, Xinhua Hospital, Shanghai Second Medical University, Shanghai 200092, China. dingguo_li@hotmail.com
Telephone: +86-21-65790000-3361 Fax: +86-21-55571294
Received: July 27, 2005
Revised: August 15, 2005
Accepted: August 22, 2005
Published online: February 28, 2006

AIM: To investigate the effect of arg-gly-asp-mannose-6 phosphate (RGD-M6P) on the activation and proliferation of primary hepatic stellate cells in vitro.

METHODS: Hepatic stellate cells (HSCs) were isolated from rats by in situ collagenase perfusion of liver and 18% Nycodenz gradient centrifugation and cultured on uncoated plastic plates for 24 h with DMEM containing 10% fetal bovine serum (FBS/DMEM) before the culture medium was substituted with 2% FBS/DMEM for another 24 h. Then, HSCs were cultured in 2% FBS/DMEM with transforming growth factor β1, M6P, RGD, or RGD-M6P, respectively. Cell morphology was observed under inverted microscope, smooth muscle α-actin (α-SMA) was detected by immunocytochemistry, type III procollagen (PCIII) in supernatant was determined by radioimmunoassay, and the proliferation rate of HSCs was assessed by flow cytometry.

RESULTS: RGD-M6P significantly inhibited the morphological transformation and the α-SMA and PCIII expressions of HSCs in vitro and also dramatically prevented the proliferation of HSCs in vitro. Such effects were remarkably different from those of RGD or M6P.

CONCLUSION: The new compound, RGD-M6P, which has a dramatic effect on primary cultured HSCs in vitro, can inhibit the transformation of HSCs in culture caused by TGFβ1, suppresses the expression of PCIII and decreases proliferation rate of HSC. RGD-M6P can be applied as a selective drug carrier targeting at HSCs, which may be a new approach to the prevention and treatment of liver fibrosis.

Keywords: RGD, Mannose-6-phosphate, Hepatic stellate cell, Liver fibrosis