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Dual expression of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase in fibrotic human livers.
Hepatology. 1997 Dec; 26(6):1521-9.Hep

Abstract

We have previously reported increased expression of matrix metalloproteinase-2 (MMP-2) using a rat model of liver fibrosis. However we did not clarify how the precursor of MMP-2 (proMMP-2) was activated. Therefore, we used human liver specimens with chronic hepatitis (CH) and liver cirrhosis (LC) to examine expression of membrane-type-1-MMP (MT1-MMP), which has recently been determined to activate proMMP-2. Northern hybridization studies showed a 5.4- and 1.4-fold increase in MMP-2 expression in CH and LC, respectively, as compared with normal liver. MT1-MMP gene expression simultaneously increased 4.0- and 1.4-fold in CH and LC, respectively. In situ hybridization using 35S-cRNA probes of MMP-2 and MT1-MMP showed prominent silver granules in elongated cells found in the lobules, periportal areas, and fibrous septa of CH and LC samples. These elongated cells expressed alpha-smooth muscle actin by immunohistochemistry. Immunoelectron microscopic examination localized MMP-2 and MT1-MMP to the rough endoplasmic reticulum of stellate cells located in the lobules and periportal areas, or to fibroblasts in the fibrous septa, suggesting that MMP-2 and MT1-MMP were produced by these cells. In addition, cytoplasmic and membranous immunodeposits of both MMPs were found in endothelial cells, Kupffer cells, capillary endothelial cells, and lymphocytes, indicating that activation of proMMP-2 occurs locally. Increased expression of MMP-2 and MT1-MMP was detected in CH and LC, while dual over-expression was found in stellate cells and fibroblasts, possibly resulting in the increase of active MMP-2 in and around these cells. These findings suggest that activated MMP-2 may remodel liver parenchyma during the process of liver fibrosis.

Authors+Show Affiliations

Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9397993

Citation

Takahara, T, et al. "Dual Expression of Matrix Metalloproteinase-2 and Membrane-type 1-matrix Metalloproteinase in Fibrotic Human Livers." Hepatology (Baltimore, Md.), vol. 26, no. 6, 1997, pp. 1521-9.
Takahara T, Furui K, Yata Y, et al. Dual expression of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase in fibrotic human livers. Hepatology. 1997;26(6):1521-9.
Takahara, T., Furui, K., Yata, Y., Jin, B., Zhang, L. P., Nambu, S., Sato, H., Seiki, M., & Watanabe, A. (1997). Dual expression of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase in fibrotic human livers. Hepatology (Baltimore, Md.), 26(6), 1521-9.
Takahara T, et al. Dual Expression of Matrix Metalloproteinase-2 and Membrane-type 1-matrix Metalloproteinase in Fibrotic Human Livers. Hepatology. 1997;26(6):1521-9. PubMed PMID: 9397993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dual expression of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase in fibrotic human livers. AU - Takahara,T, AU - Furui,K, AU - Yata,Y, AU - Jin,B, AU - Zhang,L P, AU - Nambu,S, AU - Sato,H, AU - Seiki,M, AU - Watanabe,A, PY - 1997/12/16/pubmed PY - 1997/12/16/medline PY - 1997/12/16/entrez SP - 1521 EP - 9 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 26 IS - 6 N2 - We have previously reported increased expression of matrix metalloproteinase-2 (MMP-2) using a rat model of liver fibrosis. However we did not clarify how the precursor of MMP-2 (proMMP-2) was activated. Therefore, we used human liver specimens with chronic hepatitis (CH) and liver cirrhosis (LC) to examine expression of membrane-type-1-MMP (MT1-MMP), which has recently been determined to activate proMMP-2. Northern hybridization studies showed a 5.4- and 1.4-fold increase in MMP-2 expression in CH and LC, respectively, as compared with normal liver. MT1-MMP gene expression simultaneously increased 4.0- and 1.4-fold in CH and LC, respectively. In situ hybridization using 35S-cRNA probes of MMP-2 and MT1-MMP showed prominent silver granules in elongated cells found in the lobules, periportal areas, and fibrous septa of CH and LC samples. These elongated cells expressed alpha-smooth muscle actin by immunohistochemistry. Immunoelectron microscopic examination localized MMP-2 and MT1-MMP to the rough endoplasmic reticulum of stellate cells located in the lobules and periportal areas, or to fibroblasts in the fibrous septa, suggesting that MMP-2 and MT1-MMP were produced by these cells. In addition, cytoplasmic and membranous immunodeposits of both MMPs were found in endothelial cells, Kupffer cells, capillary endothelial cells, and lymphocytes, indicating that activation of proMMP-2 occurs locally. Increased expression of MMP-2 and MT1-MMP was detected in CH and LC, while dual over-expression was found in stellate cells and fibroblasts, possibly resulting in the increase of active MMP-2 in and around these cells. These findings suggest that activated MMP-2 may remodel liver parenchyma during the process of liver fibrosis. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/9397993/Dual_expression_of_matrix_metalloproteinase_2_and_membrane_type_1_matrix_metalloproteinase_in_fibrotic_human_livers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0270913997005387 DB - PRIME DP - Unbound Medicine ER -