title: Age-related changes in matrix metalloproteinase-9 regulation in cultured mouse aortic smooth muscle cells.
abstract: We previously reported that aortic smooth muscle cells (SMC) from aged mice have an age-related decline in proliferative capacity compared with those derived from young mice. Here we investigated matrix metalloproteinase-9 (MMP-9) regulation in both young and aged SMC. Zymography, immunoblot, and northern blot analysis showed that MMP-9 expression is significantly reduced in response to tumor necrosis factor-alpha stimulation with increasing in vitro age. Mutational analysis, gel shift assays and supershift assays demonstrated that the lower MMP-9 expression in aged SMC is associated with lower activities of NF-kappaB and AP-1. Since mitogen-activated protein kinase ERK1/2 induce MMP-9 expression, we examined whether U0126, an ERK1/2 inhibitor, influenced MMP-9 expression in aged SMC. Treatment with U0126 successfully inhibited MMP-9 expression in both young and aged SMC. Finally, to analyze the causal relationship between replicative senescence and MMP-9 expression, we stably overexpressed the MMP-9 gene in aged SMC and we showed no alteration of the proliferative capacity of the transduced cells. Taken together, these results suggest that down-regulation of MMP-9 expression in SMC may play a role in vascular remodeling during in vitro aging.
authors.affiliation: National Research Laboratory for Glycobiology, Korean Ministry of Science and Technology, Kyungju, Kyungbuk 780-714, South Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Cha
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Nam
authors.forename: Marschall S
authors.initials: MS
authors.lastname: Runge
authors.forename: Cam
authors.initials: C
authors.lastname: Patterson
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta; D015152:Blotting, Northern / Q000379:methods; D002455:Cell Division; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D015870:Gene Expression; D015151:Immunoblotting / Q000379:methods; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009130:Muscle, Smooth / Q000201:enzymology*; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9