Effects of hypoxia and hyperoxia on the regulation of the expression and activity of matrix metalloproteinase-2 in hepatic stellate cell.
- Author:
Pingsheng CHEN
1
;
Weirong ZHAI
;
Yue'e ZHANG
;
Xiaomei ZHOU
;
Jinsheng ZHANG
;
Yuqin LING
;
Yinghong GU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cell Hypoxia; physiology; Hyperoxia; enzymology; Liver; cytology; enzymology; Male; Matrix Metalloproteinase 2; analysis; metabolism; Rats; Rats, Sprague-Dawley; Tissue Inhibitor of Metalloproteinase-2; analysis
- From: Chinese Journal of Pathology 2002;31(4):337-341
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the effects of hypoxia and hyperoxia on the expression and activity regulation of matrix metalloproteinase-2 (MMP-2) of the hepatic stellate cell (HSC).
METHODSThe expression of MMP-2, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and membrane type matrix metalloproteinase-1 (MT1-MMP) in cultured rat HSC under hypoxic or hyperoxic conditions were detected with immunocytochemistry (LSAB method), the contents of MMP-2, TIMP-2 in culture supernatant with ELISA and the activity of MMP-2 in supernatant with zymography.
RESULTS(1) In the situation of hypoxia for 12 h, the expression of MMP-2 increased (hypoxia group positive indexes: 5.7 +/- 2.0; control: 3.2 +/- 1.0; P < 0.01), while TIMP-2 decreased (hypoxia group positive indexes: 2.5 +/- 0.7; control: 3.6 +/- 1.0; P < 0.05) in HSC, and the activity of MMP-2 in supernatant declined obviously (hypoxia group: 7.334 +/- 1.922; control: 17.277 +/- 7.424; P < 0.01). At the different time courses of hypoxia, the change of expression and activity of MMP-2 was most notable at 6 h. (2) In the situation of hyperoxia for 12 h, the protein contents of MMP-2, TIMP-2 in supernatant were both higher than those of the control, especially the TIMP-2 (hyperoxia group A(450): 0.050 +/- 0.014; control: 0.022 +/- 0.010; P < 0.01), and so was the activity of MMP-2 (hyperoxia group total A: 5.252 +/- 0.771; control: 4.304 +/- 1.083; P < 0.05). The expression of MT1-MMP was also increased.
CONCLUSIONSThe HSC is sensitive to the oxygen. Hypoxia accelerates the expression of MMP-2 and the effect is more marked at the early stage. Hyperoxia increases the activity of MMP-2.