title: Hypoxia down-regulates secretion of MMP-2, MMP-9 in porcine pulmonary artery endothelial and smooth muscle cells and the role of HIF-1.
abstract: Primary cell culture, techniques of gene transfection, gelatin zymography, and Western blot were used to investigate the effect of hypoxia on the secretion of MMP-2 and MMP-9 in pulmonary artery endothelial cells (PAEC) and smooth muscle cells (PASMC), and the role of HIF-1. Our results showed that (1) after exposure to hypoxia for 24 h, the protein content and activity of MMP-2 in the PAEC medium as well as these of MMP-2 and MMP-9 in PASMC medium (P < 0. 01) decreased significantly in contrast to those in normoxic group (P < 0.05); (2) after transfection of wild type EPO3'-enhancer, a HIF-1 decoy, the content and activity of MMP-2 and MMP-9 in hypoxic mediums became higher than those in normoxic group (P < 0.01), while transfection of mutant EPO3'-enhancer didn't affect the hypoxia-induced down-regulation. It is concluded that hypoxia could inhibit the secretion and activity of MMP-2 and MMP-9 in PAEC and PASMC, which could be mitigated by the transfection of EPO3'-enhancer and that HIF-1 pathway might contribute to hypoxia-induced down-regulation of MMP-2 and MMP-9.
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Pulmonary Laboratory of Ministry of Health of China, Wuhan 430030, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Wanli
authors.initials: W
authors.lastname: Ma
authors.forename: Dan
authors.initials: D
authors.lastname: Ke
authors.forename: Xianrong
authors.initials: X
authors.lastname: Jin
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Liu
authors.forename: Dixun
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology*; D004742:Enhancer Elements, Genetic; D004921:Erythropoietin / Q000235:genetics / Q000494:pharmacology; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D011651:Pulmonary Artery / Q000166:cytology / Q000201:enzymology; D013552:Swine
chemical_list: D051793:Hypoxia-Inducible Factor 1; D004921:Erythropoietin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9