Integrin-linked kinase induces both senescence-associated alterations and extracellular fibronectin assembly in aging cardiac fibroblasts.
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 beta-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.
Chen
Xiangmei
X
Department of Nephrology, Kidney Center and Key Lab of PLA, Chinese General Hospital of PLA, Beijing, PR China. xmchen@public.bta.net.cn
Li
Zhihui
Z
Feng
Zhe
Z
Wang
Jianzhong
J
Ouyang
Chun
C
Liu
Weiping
W
Fu
Bo
B
Cai
Guangyan
G
Wu
Chuanyue
C
Wei
Ribao
R
Wu
Di
D
Hong
Quan
Q
D000256:Adenoviridae; D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000032:analysis; D005347:Fibroblasts / Q000502:physiology; D005353:Fibronectins / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D009206:Myocardium / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D000099200:Scaffold Protein ILK
D003598:Cytoskeletal Proteins; D005353:Fibronectins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK