Matrilysin (MMP-7) is a major matrix metalloproteinase upregulated in biliary atresia-associated liver fibrosis.
Matrix metalloproteinases (MMPs) are the proteases responsible for tissue remodeling during liver fibrosis caused by various disorders including biliary atresia. However, information regarding the relative contribution of these proteases to liver fibrosis is still limited. We studied matrix metalloproteinase-2 (MMP-2), -7, -9 and -13 mRNA expressions in the liver tissue of early-stage biliary atresia at the time of Kasai's procedure, late-stage biliary atresia at the time of liver transplantation with advanced fibrosis and nondiseased control without liver fibrosis. The results of real-time quantitative reverse transcriptase-PCR analysis revealed that only MMP-2 and -7 expressions were significantly different between groups. MMP-2 was significantly higher in Liver Transplantation group than both in Control (P=0.010) and in Kasai's Procedure (P=0.001) groups, whereas the difference of MMP-2 expression between Control and Kasai's Procedure was not significant. However, the relative expression level of MMP-7 was sequentially elevated when comparing Control, Kasai's Procedure and Liver Transplantation groups, and there was significant (P=0.019) difference when comparing Control and Liver Transplantation groups. Moreover, the fold difference in MMP-7 mRNA was much higher than that in MMP-2 mRNA between groups. The expressions of MMP-7 were further confirmed by agarose gel electrophoresis and Western blotting. Immunohistochemical analysis revealed a significant positive correlation of the scores of MMP-7 immunostaining with the stages of liver fibrosis. In situ hybridization demonstrated that the bile ductular epithelial cells, Kupffer cells and hepatocytes were the major producers of matrix metalloproteinase-7 in the liver. Our results imply that MMP-7 is a major MMP associated with the tissue remodeling during the progression of liver fibrosis in biliary atresia.
Huang
Chao-Cheng
CC
Graduate Institute of Clinical Medical Sciences, Chang Gung University, Lin-Ko, Taiwan.
Chuang
Jiin-Haur
JH
Chou
Ming-Huei
MH
Wu
Chia-Lin
CL
Chen
Ching-Mei
CM
Wang
Chih-Chi
CC
Chen
Yaw-Sen
YS
Chen
Chao-Long
CL
Tai
Ming-Hong
MH
D000293:Adolescent; D000328:Adult; D001656:Biliary Atresia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D002648:Child; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D007728:Kupffer Cells / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation
D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2