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Interferon‐β induces cellular senescence in vascular smooth muscle cells
Author(s) -
Byeon Hyeeun,
Rhee DongKwon,
Pyo Suhkneung
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.750.11
Subject(s) - senescence , cell cycle , interferon , vascular smooth muscle , cell cycle checkpoint , microbiology and biotechnology , g1 phase , western blot , telomerase , biology , telomere , telomerase reverse transcriptase , cell , chemistry , immunology , endocrinology , biochemistry , dna , gene , smooth muscle
Interferon‐¥â(IFN‐¥â) is one of the type‐¥° interferon with potent antiviral and anti‐proliferative activities. Previous studies have documented that IFN‐¥â induces p53‐dependent senescence. However, the mechanism of IFN‐¥â‐induced cellular senescence remains unclear. In the present study, we examined the mechanism by which IFN‐¥â induced cellular senescence in vascular smooth muscle cells (VSMCs). Cells treated with IFN‐¥â (500~2000U/ml) under serum free condition was arrested in G1 phase of cell cycle. In addition, treatment with IFN‐¥â resulted in increased in senescence‐associated ¥â‐galactosidase (SA‐¥â‐gal) activity and PAI‐1 expression. Western blot analysis revealed that IFN‐β treatment up‐regulated p53 expression and its phosphorylation, whereas mdm2 expression was decreased. We also examined the effect of IFN‐β treatment on other cell cycle related proteins such as p21 and CDK2. The expression of p21 was increased in cells treated with IFN‐β accompanied by down‐regulation of CDK2, which supported the G1 phase arrest. Moreover, the decreased mRNA level of TERT (Telomerase Reverse Transcriptase) by IFN‐β was confirmed by RT‐PCR. Taken together, the present data suggest that IFN‐β regulates the levels of cell cycle‐related proteins and G1 phase cell cycle arrest, leading to induction of the senescence‐like arrest of VSMCs.