Gene expressions and roles of matrix metalloproteinases-8 and tissue inhibitor of metalloproteinases-1 in hyperoxia-induced pulmonary fibrosis in neonatal rats
FU Jian-Hua, XUE Xin-Dong
Department of Pediatrics, Second Affiliated Hospital, China Medical University, Shenyang 110004, China
Abstract：OBJECTIVE: Extracellular matrix (ECM) deposition is a major reason of pulmonary fibrosis in hyperoxia-induced lung injury. However, the relevant mechanism has not been identified. This study examined the gene expressions of matrix metalloproteinases-8 (MMP-8, a catabolic enzyme of type I collagen) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in neonatal rats with hyperoxi-induced pulmonary injury in order to explore the role of MMP-8 and TIMP-1 in pulmonary fibrosis. METHODS: Eighty term newborn rats were randomly exposed to hyperxia (FiO2=0.90, hyperxia group) and to room air (FiO2=0.21, control group) (n =40 each). Lung injury was induced by hyperxia exposure. The content of type I collagen and the expressions of type I collagen protein and MMP-1 mRNA and TIMP-1 mRNA were assayed with enzyme linked immunoadsorbent (ELISA), immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) respectively on days 1, 3, 7, 14 and 21 after exposure. RESULTS: The content of type I collagen and the expression of type I collagen protein in the hyperxia group were statistically higher than those in the control group at 14 and 21 days post-exposure. The MMP-8 mRNA expression decreased while the TIMP-1 mRNA expression increased significantly in the hyperxia group as compared to the control group at 14 and 21 days post-exposure. CONCLUSIONS: Hyperxia exposure down-regulates MMP-8 mRNA expression and up-regulates TIMP-1 mRNA expression. This results in a reduction of ECM degradation, thereby ECM deposition occurs in lung tissue, which may be an important mechanism of pulmonary fibrosis following hyperoxia-induced lung injury.［Chin J Contemp Pediatr, 2007, 9 (1):1- 5］
FU Jian-Hua,XUE Xin-Dong. Gene expressions and roles of matrix metalloproteinases-8 and tissue inhibitor of metalloproteinases-1 in hyperoxia-induced pulmonary fibrosis in neonatal rats[J]. CJCP, 2007, 9(1): 1-5.
