Abstract: Objective To study the effects of hypoxia on collagen synthesis and mRNA expression in systemic scleroderma(SSc)and normal dermal fibroblasts.Methods Skin specimens were resected from 5 SSc patients and 5 normal human controls.Fibroblasts were isolated from the specimens,and subjected to primary culture and passage.Then,the cells were exposed to either low(2%)or standard(20%)oxygen tension for 3 to 6 days.The collagen production level in the cultured medium was calculated based on hydroxyproline level detected by speetro-photometry.RT-PCR was used to detect the mRNA expression of proαl(Ⅰ)and proαl(Ⅲ)collagen in the fibroblasts.Results At the end of the 6th day,the concentration of collagen was significantly higher under hypoxia condition than that under normoxic condition,in the cul-tured medium of both SSc(t=3.973,P=0.0041)and normal(t=2.630,P=0.0302)skin fibroblasts. At the end of 3rd day,the mRNA expression levels of both proαl(Ⅰ)and proαl(Ⅲ)collagen were signifi-cantly higher in hypoxia condition than in normoxic condition in both SSc(typeⅠ:t=5.811,P=0.0004; typeⅢ:t=6.442,P=0.0002)and normal(typeⅠ:t=4.396,P=0.0023;typeⅢ:t=2.237,P=0.0453) skin fibroblasts.Conclusions Under hypoxia condition,the collagen synthesis,typeⅠand typeⅢprocol-lagen mRNA expression are all increased in SSc and normal skin fibroblasts.Hypoxia may be a contributory factor in skin sclerosis.

Key words: Scleroderma, systemic, Fibroblasts, Anoxia, Collagen