Retinoic Aacid Diminished the Expression of MMP-2 in Hyperoxia-exposed Premature Rat Lung Fibroblasts through Regulating Mitogen-activated Protein Kinases

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 31; no. 2; pp. 251 - 257
• Main Author: 李文斌 常立文 容志惠 刘伟
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.04.2011; Department of Pediatrics, Tongji Hospital, Tongji Medical University, Huazhong University of Science and Technology, Wuhan 430030, China
• Subjects: Medicine; Medicine & Public Health; MMP; PD98059; 半定量逆转录聚合酶链反应; 基质金属蛋白酶-2; 有丝分裂原活化蛋白激酶; 维甲酸; 肺成纤维细胞; 高氧; retinoic acid; matrix metalloproteinase-2; hyperoxia; premature rats; lung fibroblasts; mitogen-activated protein kinases
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-011-0262-1

This study examined the effects of retinoic acid （RA）, PD98059, SP600125 and SB203580 on the hyperoxia-induced expression and regulation of matrix metalloproteinase-2 （MMP-2） and metalloproteinase-2 （TIMP-2） in premature rat lung fibroblasts （LFs）. LFs were exposed to hyperoxia or room air for 12 h in the presence of RA and the kinase inhibitors PD98059 （ERK1/2）, SP600125 （JNK1/2） and SB203580 （p38） respectively. The expression levels of MMP-2 and TIMP-2 mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction （RT-PCR）. MMP-2 activity was measured by zymography. The amount of p-ERK1/2, REK1/2, p-JNK1/2, JNK1/2, p-p38 and p38 was determined by Western blotting. The results showed that： （1） PD98059, SP600125 and SB203580 significantly inhibited p-ERK1/2, p-JNK1/2 and p-p38 respectively in LFs; （2） The expression of MMP-2 mRNA in LFs exposed to hyperoxia was decreased after treatment with RA, SP600125 and SB203580 respectively （P0.01 or 0.05）, but did not change after treatment with PD98059 （P0.05）. Meanwhile, RA, PD98059, SP600125 and SB203580 had no effect on the expression of TIMP-2 mRNA in LFs exposed to room air or hyperoxia （P0.05）; （3） The expression of pro- and active MMP-2 experienced no change after treatment with RA or SP600125 in LFs exposed to room air （P0.05）, but decreased remarkably after hyperoxia （P0.01 or 0.05）. SB203580 inhibited the expression of pro- and active MMP-2 either in room air or under hyperoxia （P0.01）. PD98059 exerted no effect on the expression of pro- and active MMP-2 （P0.05）. It was suggested that RA had a protective effect on hyperoxia-induced lung injury by down-regulating the expression of MMP-2 through decreasing the JNK and p38 activation in hyperoxia.