In vitro cellular aging is associated with enhanced proliferative capacity, G1 cell cycle modulation, and matrix metalloproteinase-9 regulation in mouse aortic smooth muscle cells.
In vitro cellular aging is associated with enhanced proliferative capacity, G1 cell cycle modulation, and matrix metalloproteinase-9 regulation in mouse aortic smooth muscle cells.
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体外细胞衰老与小鼠主动脉平滑肌细胞的增殖能力增强、G1 细胞周期调节和基质金属蛋白酶 9 调节相关。
DOI：
10.1016/s0003-9861(03)00402-8
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发表时间：
2003
影响因子：
3.9
通讯作者：
Cheorl
中科院分区：
文献类型：
--
作者：
S. Moon;Byung‐Yoon Cha;Cheorl
研究了年轻（第1-3代）和老年（第25-30代）小鼠主动脉平滑肌细胞（MASMC）的细胞和分子事件。免疫印迹和免疫荧光分析表明，平滑肌α-肌动蛋白（SM α-actin）水平显着降低，随着年龄的增长，在体外。与年轻的MASMC相比，老年MASMC对胎牛血清（FBS）的增殖能力增加。细胞周期相关蛋白如cyclin D1、cyclin E、CDK 2和CDK 4以及与CDK 2和CDK 4相关的激酶活性在老化MASMC中增加。此外，衰老细胞中CDK抑制剂p21升高，而p27降低。G1期细胞周期机制的这些变化可以通过增加的增殖能力来解释。基质金属蛋白酶-9（MMP-9）的表达也随着肿瘤坏死因子-α（TNF-α）的作用而增加，如酶谱和免疫印迹分析所证实的。瞬时转染试验显示，MMP-9启动子活性对TNF-α的应答转录呈年龄依赖性增加。此外，通过突变分析和凝胶迁移实验，鉴定了参与TNF-α对老年MASMC MMP-9调控的转录因子NF-κB和AP-1。这些结果表明，与年龄相关的SMC增殖能力的增加，积累细胞周期调节剂，MMP-9的表达可能在血管重塑在体外老化过程中发挥作用。
Cellular and molecular events in young (passage 1–3) and aged (passage 25–30) primary mouse aortic smooth muscle cells (MASMC) were investigated. Immunoblot and immunofluorescence analyses indicated that smooth muscle α-actin (SM α-actin) levels were significantly reduced with increasing in vitro age. Aged MASMC showed an increased proliferative capacity in response to fetal bovine serum (FBS) in comparison with young MASMC. The cell cycle-associated proteins such as cyclin D1, cyclin E, CDK2, and CDK4, and kinase activities associated with CDK2 and CDK4 were increased in aged MASMC. In addition, CDK inhibitor p21 was elevated in aged cell, whereas p27 was decreased. These changes of G1 cell cycle machinery could be explained by the increased proliferative capacity. Matrix metalloproteinase-9 (MMP-9) expression was also increased in response to tumor necrosis factor-α (TNF-α) in aged MASMC, as evidenced by zymography and immunoblot analysis. Transient transfection assays showed an age-dependent increase in transcription from MMP-9 promoter activity in response to TNF-α. In addition, the transcription factors NF-κB and AP-1 that are involved in the MMP-9 regulation of aged MASMC in response to TNF-α were identified by means of mutation analysis and gel shift assays. These results suggest that the age-associated increase in SMC proliferative capacity, accumulative cell cycle regulators, and MMP-9 expression may play a role in vascular remodeling during in vitro aging.
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影响因子：
10.5
作者：
LaBaer, J;Garrett, MD;Harlow, E
通讯作者：
Harlow, E
DOI：
10.1111/j.1365-201x.1998.tb10706.x
发表时间：
1998-12-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
Owens, GK
通讯作者：
Owens, GK
影响因子：
20.1
作者：
GALIS, ZS;MUSZYNSKI, M;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
33.6
作者：
G. Owens
通讯作者：
G. Owens
影响因子：
10.8
作者：
A. Rivard;N. Principe;V. Andrés
通讯作者：
A. Rivard;N. Principe;V. Andrés