[Effects of hypoxia and hyperoxia on the regulation of the expression and activity of matrix metalloproteinase-2 in hepatic stellate cell].
OBJECTIVE
To 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).


METHODS
The 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.


CONCLUSIONS
The 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.
Chen
Pingsheng
P
Department of Pathology, Medical College, Fudan University, Shanghai, 200032, China.
Zhai
Weirong
W
Zhang
Yue'e
Y
Zhou
Xiaomei
X
Zhang
Jinsheng
J
Ling
Yuqin
Y
Gu
Yinghong
Y
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D018496:Hyperoxia / Q000201:enzymology*; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis
D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2