title: Retinoic acid diminished the expression of MMP-2 in hyperoxia-exposed premature rat lung fibroblasts through regulating mitogen-activated protein kinases.
abstract: 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 (P<0.01 or 0.05), but did not change after treatment with PD98059 (P>0.05). Meanwhile, RA, PD98059, SP600125 and SB203580 had no effect on the expression of TIMP-2 mRNA in LFs exposed to room air or hyperoxia (P>0.05); (3) The expression of pro- and active MMP-2 experienced no change after treatment with RA or SP600125 in LFs exposed to room air (P>0.05), but decreased remarkably after hyperoxia (P<0.01 or 0.05). SB203580 inhibited the expression of pro- and active MMP-2 either in room air or under hyperoxia (P<0.01). PD98059 exerted no effect on the expression of pro- and active MMP-2 (P<0.05). 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.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical University, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical University, Huazhong University of Science and Technology, Wuhan, 430030, China. lwchang@tjh.tjmu.edu.cn.
authors.forename: Liwen
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical University, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Rong
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical University, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D015536:Down-Regulation; D005333:Fetus; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D008168:Lung / Q000166:cytology*; D055370:Lung Injury / Q000517:prevention & control; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D014212:Tretinoin; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat