Hypoxic conditions decrease the mRNA expression of proalpha1(I) and (III) collagens and increase matrix metalloproteinases-1 of dermal fibroblasts in three-dimensional cultures.
The effect of hypoxia on the expression of extracellular matrix-related genes by human dermal fibroblasts was investigated using a novel three-dimensional culture supplemented with L-ascorbic acid 2-phosphate. Experiments were performed by placing replicate dishes in either hypoxic (2%) or in normoxic (20%) condition for various periods of time ranging up to 72 h. The mRNA expression levels of proalpha1(I), proalpha1(III) collagens and MMP-1 were analyzed using Northern blotting. Hypoxia transiently increased proalpha1(I) and proalpha1(III) collagen gene expression at 24 h, but a prolonged exposure to hypoxia decreased them. A slight increase in MMP-1 mRNA was observed at 24 h and prolonged exposure for up 72 h resulted in significantly increased expression of MMP-1 gene. Our results suggest that enhanced degradation as well as decreased synthesis of collagens induced by hypoxia may account for the delayed wound healing associated with circulatory disturbances.
Yamanaka
M
M
Department of Dermatology, Gunma University School of Medicine, 3-39-22, Showa-machi, Maebashi, 371-8511, Gunma, Japan. myamanak@sb.gunma-u.ac.jp
Ishikawa
O
O
D000199:Actins / Q000235:genetics; D002478:Cells, Cultured; D003584:Cytological Techniques; D005347:Fibroblasts / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D011347:Procollagen / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology
D000199:Actins; D011347:Procollagen; D012333:RNA, Messenger; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D020781:Matrix Metalloproteinase 1