Matrilysin (MMP-7) is a major matrix metalloproteinase upregulated in biliary atresia-associated liver fibrosis

Abstract

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 ¼ 0.010) and in Kasai's Procedure (P ¼ 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 ¼ 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. Modern Pathology (2005) 18, 941-950.

A novel nonsynonymous variant of matrix metalloproteinase-7 confers risk of liver cirrhosis

“…Similarly, MMP-7 releases from the epithelial cells to the lumen of bile duct in cirrhotic liver and can be strongly detected in the bile plugs of the lumens. 28 These imply a role of MMP-7 in the tissue repair process. Results from the current study demonstrated that the A allele encoding MMP-7(Asp-137) is a gain-of-function allele.…”

Renal Allografts with IF/TA Display Distinct Expression Profiles of Metzincins and Related Genes

“…(8). The latter are the best characterized proteases involved in ECM remodeling (9,10), and they have been studied in conditions like inflammation, cancer, arteriosclerosis and fibrosis (11)(12)(13)(14)(15). Most …”

Matrix Metalloproteinase-7 as a Surrogate Marker Predicts Renal Wnt/β-Catenin Activity in CKD

“…In that regard, MMP-7 has been identified as a major proteinase upregulated in billary atresia-associated liver fibrosis, and its expression is thought to best discriminate between cirrhosis and precirrhotic stages. 10,11 Induction of MMP-7 also occurs in human idiopathic pulmonary fibrosis, and it has been postulated as a potential peripheral blood biomarker for disease progression. 12,13 As for the kidney, an earlier study documented an increased expression of MMP-7 in polycystic kidney disease, acute kidney injury induced by folic acid, and obstructive nephropathy.…”