Evaluation of matrix metalloproteinases and their endogenous tissue inhibitors in biliary atresia–associated liver fibrosis

Integrin αvβ6 and Mediators of Extracellular Matrix Deposition Are Up-Regulated in Experimental Biliary Atresia

“…Somewhat surprisingly, there was a much greater increase (69-fold) of metalloproteinase (MMP)-7. However, this is consistent with MMP-7 mRNA expression seen in human samples [4]. At 14 d, TIMP-1 mRNA was further increased (48-fold), as was MMP-7 expression compared with age-matched control mice (Fig.…”

“…Furthermore, on day 14 PAI-1 expression was greatly increased, and smaller but statistically significant increases in TIMP-4 and MMP-9 were found. In a study using microarrays in human tissue, a similar pattern was found [4]. MMP-7 expression increased with progression of liver fibrosis and MMP-9 was upregulated at the time of Kasai procedure but not at liver transplantation.…”

“…Recent evidence using a bile duct ligation model suggests that transforming growth factor-beta (TGF-␤) and its upstream mediator integrin ␣ v ␤ 6 are central to the development hepatic fibrosis after biliary obstruction [3]. Therefore, we proposed to evaluate these same factors and known downstream mediators of TGF-␤ function, including the plasminogen-activator inhibitors (PAIs) and the tissue inhibitors of matrix metalloproteinases (TIMPs) in a model of biliary atresia [4].…”

Immunological investigation of the hepatic tissue from infants with biliary atresia

“…Significant upregulation of MMP-9 in the early stage of biliary atresia was also found in the same study [19]. Rapid upregulation of MMP-9 has also been demonstrated in previous animal studies of biliary atresia [4,20].…”

Closing in on Biliary Atresia

“…Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) are major proteases responsible for remodeling liver tissue. Differential expression of MMPs and TIMPs in different stages of BA was found on DNA microarray analysis and confirmed on real time PCR, suggesting a role for these proteins in the remodeling of liver tissue during the progress of BA-associated liver fibrosis [15].…”