Herbal compound 861 regulates mRNA expression of collagen synthesis- and degradation-related genes in human hepatic stellate cells.
OBJECTIVE
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 types I and 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 beta1 (TGF-beta1) in cultured-activated HSCs treated with Cpd 861 or interferon-gamma (IFN-gamma) were determined by real-time PCR.


RESULTS
Both Cpd 861 and IFN-gamma reduced the mRNA levels of collagen type III, MMP-2 and TGF-beta1. 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.


CONCLUSIONS
The anti-fibrosis function of Cpd 861 may be mediated by both decreased interstitial collagen sythesis by inhibiting the transcription of collagen type III and TGF-beta1 and increased degradation of these collagens by up-regulating MMP-1 and down-regulating TIMP-1 mRNA levels.
Wang
Lin
L
Beijing Genomic Institute, Beijing 101300, China.
Wang
Bao-En
BE
Wang
Jian
J
Xiao
Pei-Gen
PG
Tan
Xue-Hai
XH
D002460:Cell Line; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D024042:Collagen Type I; D024061:Collagen Type III; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C476499:herbal compound 861; D007371:Interferon-gamma; D003094:Collagen; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14