Hypoxia down-regulates secretion of MMP-2, MMP-9 in porcine pulmonary artery endothelial and smooth muscle cells and the role of HIF-1.
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.
Ye
Hong
H
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Pulmonary Laboratory of Ministry of Health of China, Wuhan 430030, China.
Zheng
Yanfang
Y
Ma
Wanli
W
Ke
Dan
D
Jin
Xianrong
X
Liu
Shengyuan
S
Wang
Dixun
D
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
D051793:Hypoxia-Inducible Factor 1; D004921:Erythropoietin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9