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World J Gastroenterol. Mar 21, 2008; 14(11): 1790-1794
Published online Mar 21, 2008. doi: 10.3748/wjg.14.1790
Herbal compound 861 regulates mRNA expression of collagen synthesis- and degradation-related genes in human hepatic stellate cells
Lin Wang, Bao-En Wang, Jian Wang, Pei-Gen Xiao, Xue-Hai Tan
Lin Wang, Jian Wang, Xue-Hai Tan, Beijing Genomic Institute, Beijing 101300, China
Lin Wang, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 101300, China
Bao-En Wang, Liver Research Center, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing 101300, China
Pei-Gen Xiao, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 101300, China
Author contributions: Wang L, Wang BE, Wang J, Xiao PG and Tan XH designed the research; Wang BE formulated the Cpd 861; Wang L performed the research; Wang L, Wang BE and Tan XH wrote the paper.
Correspondence to: Dr. Xue-Hai Tan, Beijing Genomic Institute, Beijing 101300, China. tanxh@genomics.org.cn
Telephone: +86-10-80481755
Fax: +86-10-80498676
Received: October 24, 2007
Revised: January 14, 2008
Published online: March 21, 2008
Abstract

AIM: To identify the role of herbal compound 861 (Cpd 861) in the regulation of mRNA expression of collagen synthesis- and degradation-related genes in human hepatic stellate cells (HSCs).

METHODS: mRNA levels of collagen typesIand III, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 2 (MMP-2), membrane type-1 matrix metalloproteinase (MT1-MMP), tissue inhibitor of metalloproteinase 1 (TIMP-1), and transforming growth factor β1 (TGF-β1) in cultured-activated HSCs treated with Cpd 861 or interferon-γ (IFN-γ) were determined by real-time PCR.

RESULTS: Both Cpd 861 and IFN-γ reduced the mRNA levels of collagen type III, MMP-2 and TGF-β1. Moreover, Cpd 861 significantly enhanced the MMP-1 mRNA levels while down-regulated the TIMP-1 mRNA expression, increasing the ratio of MMP-1 to TIMP-1 to (6.3 + 0.3)- fold compared to the control group.

CONCLUSION: The anti-fibrosis function of Cpd 861 may be mediated by both decreased interstitial collagen synthesis by inhibiting the transcription of collagen type III and TGF-β1 and increased degradation of these collagens by up-regulating MMP-1 and down-regulating TIMP-1 mRNA levels.

Keywords: Herbal Compound 861, Human hepatic stellate cells, Collagen synthesis and degration, Collagen type III, Matrix metalloproteinase 1, Tissue inhibitor of metalloproteinase 1