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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 61:1232-1245 (2006)
© 2006 The Gerontological Society of America

Integrin-Linked Kinase Induces Both Senescence-Associated Alterations and Extracellular Fibronectin Assembly in Aging Cardiac Fibroblasts

Xiangmei Chen, Zhihui Li, Zhe Feng, Jianzhong Wang, Chun Ouyang, Weiping Liu, Bo Fu, Guangyan Cai, Chuanyue Wu, Ribao Wei, Di Wu and Quan Hong

1 Department of Nephrology, Kidney Center & Key Lab of PLA, Chinese General Hospital of PLA, Beijing.
2 Department of Pathology, University of Pittsburgh, Pennsylvania.

Address correspondence to Xiangmei Chen, MD, PhD, Department of Nephrology, Kidney Center and Key Lab of PLA, Chinese General Hospital of PLA, Fuxing Road 28, Beijing 100853, P.R. China. E-mail: xmchen{at}public.bta.net.cn

Integrin-linked kinase (ILK) is an integrin-binding cytoplasmic protein that is involved in regulating numerous cellular processes and extracellular matrix accumulation. We reported that ILK may be involved in cellular senescence, but whether ILK is the cause of senescence or an accompanying phenomenon still remains to be explored. Here, RNA interference and gene transfer techniques were used to knock down and overexpress ILK in 3-month-old and 28-month-old rat primary cardiac fibroblasts. The results show that, in younger cells, ILK overexpression induces larger cell shapes, lower proliferation capacity, and higher levels of enzymatic ß-galactosidase activity, and increases basal p53 and p21 protein levels, whereas knock-down of ILK prevents phenotypic changes typical of senescence in aging cells. In addition, ILK could induce the cytoskeleton proteins to organize into dense, thick bundles of filaments, which contribute to cellular enlargement and extracellular fibronectin assembly. The results indicate that ILK can accelerate the process of cellular senescence.




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Copyright © 2006 by The Gerontological Society of America.