| Involvement of RAGE, MAPK and NF-κB pathways in AGEs-induced MMP-9 activation in HaCaT keratinocytes. | |
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MedLine Citation:
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PMID: 22229442 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Advanced glycation end products (AGEs) exert divergent effects on the pathogenesis of diabetes complications. Excessive expression of matrix metalloproteinases-9 (MMP-9) is deleterious to the cutaneous wound-healing process in the context of diabetes. However, the effect of AGEs on MMP-9 induction in skin cells and the exact molecular mechanisms involved are still poorly understood. In this study, we investigated the effect of AGEs on the production of MMP-9 in HaCaT keratinocytes and characterized the signal transduction pathways activated by AGEs that are involved in MMP-9 regulation. We showed that AGE-BSA increased MMP-9 expression in HaCaT cells at both the protein and mRNA levels. The stimulatory effect of AGE-BSA on MMP-9 was attenuated by inhibitors of extracellular-signal-regulated kinase (ERK1/2, U0126), p38 mitogen-activated protein kinase (MAPK, SB203580) and NF-κB, but not c-Jun N-terminal kinase. Furthermore, receptor for advanced glycation end products (RAGE) was expressed in keratinocytes, and incubation with AGE-BSA resulted in a significant upregulation of RAGE expression in a dose-dependent manner. Silencing of the RAGE gene prevented AGE-BSA-induced MMP-9 activation and the phosphorylation of ERK1/2 and p38 MAPK. We also observed the involvement of NF-κB in AGE-BSA-induced MMP-9 activation, which was not blocked by U0126 and SB203580. These results suggest that AGEs may play an important role in the impairment of diabetic wound healing by upregulating MMP-9 expression in keratinocytes via the RAGE, ERK1/2 and p38 MAPK pathways; activation of NF-κB is also involved in this process. These pathways may represent potential targets for drug interventions to improve diabetic wound healing, a process in which MMP-9 plays a critical role. |
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Authors:
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Ping Zhu; Meng Ren; Chuan Yang; Yong-Xuan Hu; Jian-Min Ran; Li Yan |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Experimental dermatology Volume: 21 ISSN: 1600-0625 ISO Abbreviation: Exp. Dermatol. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9301549 Medline TA: Exp Dermatol Country: Denmark |
Other Details:
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Languages: eng Pagination: 123-9 Citation Subset: IM |
Copyright Information:
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© 2011 John Wiley & Sons A/S. |
Affiliation:
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Department of Endocrinology, Guangzhou Red Cross Hospital, The Fourth Affiliated Hospital, Ji'nan University, Guangzhou, China Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. |
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