Gene expressions and roles of matrix metalloproteinases-8 and tissue inhibitor of metalloproteinases-1 in hyperoxia-induced pulmonary fibrosis in neonatal rats.
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 hyperoxia-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 hyperoxia (FiO2=0.90, hyperoxia group)and to room air (FiO2=0.21, control group)(n=40 each). Lung injury was induced by hyperoxia 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 hyperoxia 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 hyperoxia group as compared to the control group at 14 and 21 days post-exposure.


CONCLUSIONS
Hyperoxia 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.
Fu
Jian-Hua
JH
Department of Pediatrics, Second Affiliated Hospital, China Medical University, Shenyang 110004, China.
Xue
Xin-Dong
XD
D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D024042:Collagen Type I / Q000032:analysis / Q000235:genetics; D005260:Female; D018496:Hyperoxia / Q000150:complications*; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000502:physiology*
D024042:Collagen Type I; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020784:Matrix Metalloproteinase 8