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Retinoic aacid diminished the expression of MMP-2 in hyperoxia-exposed premature rat lung fibroblasts through regulating mitogen-activated protein kinases

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Summary

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.

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Authors and Affiliations

  1. Department of Pediatrics, Tongji Hospital, Tongji Medical University, Huazhong University of Science and Technology, Wuhan, 430030, China

    Wenbin Li  (李文斌), Liwen Chang  (常立文), Zhihui Rong  (容志惠) & Wei Liu  (刘 伟)

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  1. Wenbin Li  (李文斌)
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  2. Liwen Chang  (常立文)
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  3. Zhihui Rong  (容志惠)
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  4. Wei Liu  (刘 伟)
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Correspondence to Liwen Chang  (常立文).

Additional information

This project was supported by a grant from the Nature Sciences Foundation of China (No. 30872795).

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Li, W., Chang, L., Rong, Z. et al. Retinoic aacid diminished the expression of MMP-2 in hyperoxia-exposed premature rat lung fibroblasts through regulating mitogen-activated protein kinases. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 31, 251–257 (2011). https://doi.org/10.1007/s11596-011-0262-1

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  • DOI: https://doi.org/10.1007/s11596-011-0262-1

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