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The Effects of Adrenomedullin on Collagen Synthesis and Transforming Growth Factor β1 Production of Human Embryonic Lung Fibroblasts in Hypoxia
Shu-Ling Hao, Zhong-He Yu*, Bao-Shen Qi1, Ji-Zheng Luo, Xiao-Mei Zhou1
Department of Respiratory Disease, General Hospital of Beijing Division, People抯 Liberation Army, Beijing 100700, China; 1Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005,
Abstract: To determine the effects of adrenomedullin (ADM)， a vasrelaxant peptide on the collagen synthesis and transforming growth factor β1 (TGF-β1) production of human embryonic lung fibroblasts in hypoxia. Human embryonic lung fibroblasts were cultured by outgrowth in vitro. Cells were exposed to hypoxia (2%O2) or normoxia after added ADM 10-9、10-8、10-7 mol/L. Total collagen synthesis and secretion were detected by [3H]-proline incorporation. TGF-β1 production in culture supernatant were measured by ELISA. Compared to normoxia， hypoxia increased fibroblasts collagen synthesis and secretion and TGF-β1 production. When exposed to hypoxia for 24 h and 72 h， collagen synthesis and secretion in ADM(10-7 mol/L) group were decreased by 19.24% and 20.76%(P<0.01)， 9.57%(P<0.05) and 10.98%(P<0.01). Hypoxia for 48 h， collagen synthesis were inhibited by ADM(10-9，10-8 and 10-7 mol/L) of 5.57%(P<0.05) and 9.19%(P>0.05)，11.09%(P<0.01) and 14.49%(P<0.05)， 35.41%(P<0.01) and 18.57%(P<0.05) respectively， in a dose-dependent manner. Hypoxia for 48 h and 72 h， TGF-β1 production were suppressed by 17.53% and 19.49% in ADM(10-7 mol/L) group (P<0.05). In hypoxia， ADM influence the process of pulmonary vascular remodeling and wound healing by inhibiting collagen synthesis of fibroblasts. ADM may be a antagonistic substance of TGF-β1.
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