Abstract
Id proteins (inhibitors of differentiation), which are involved in the control of cell cycle progression, can delay cellular differentiation and senescence and have been implicated in angiogenesis. The regulation of Id proteins in endothelial cells (ECs) by proangiogenic statins has not been investigated yet and remains unresolved. In this study, human dermal microvascular ECs (HDMECs) were stimulated with fluvastatin, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and serum in vitro. The regulation of Id1, Id3, p21, p27, and p53 and the phosphorylation of AKT was investigated by Western blotting. Id1 was up-regulated by fluvastatin and serum, but not by VEGF and HGF. Fluvastatin did not regulate p21 and p27, but down-regulated Id3 and p53 slightly. In contrast to VEGF and HGF, fluvastatin did not result in AKT phosphorylation, indicating that this pathway is not involved in the control of endothelial Id1 expression. These experiments demonstrate for the first time that Id1 can be up-regulated and p53 down-regulated by a statin in HDMECs. Regulation of these proteins in ECs may account for the proangiogenic effect of statins.
References
Nov 1, 1991·Molecular and Cellular Biology·X H SunD Baltimore
Dec 1, 1991·Molecular and Cellular Biology·R B WilsonT Kadesch
Mar 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·B A ChristyD Nathans
Jan 1, 1990·Annals of the New York Academy of Sciences·R BenezraH Weintraub
Jun 1, 1995·European Journal of Immunology·K B MeyerS Pettersson
Feb 23, 1995·The New England Journal of Medicine·C B TreasureR W Alexander
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·M V BaroneL Philipson
Jan 1, 1997·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Y JenR Benezra
Feb 7, 1997·Cell·A J Levine
Sep 7, 1999·Journal of the American Society of Nephrology : JASN·R H WeissA Joo
Oct 21, 1999·Biochemical and Biophysical Research Communications·J PammerE Tschachler
Oct 28, 1999·Nature·D LydenR Benezra
Dec 2, 1999·Genes & Development·S R DattaM E Greenberg
Apr 29, 2000·Circulation Research·M Morales-RuizW C Sessa
Sep 6, 2000·Nature Medicine·Y KureishiK Walsh
Mar 29, 2001·Nature Immunology·G BainC Murre
Mar 10, 2001·The American Journal of Pathology·X XinM E Gerritsen
Jun 20, 2001·Circulation·M VasaS Dimmeler
Jul 27, 2001·Carcinogenesis·C DenoyelleC Soria
Feb 13, 2002·Circulation·Michael WeisJohn P Cooke
Feb 13, 2002·Oncogene·R BenezraD Lyden
Apr 6, 2002·Circulation Research·Carmen UrbichStefanie Dimmeler
Apr 16, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Loïc VincentLi Hong
Jun 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Farhad R DaneshYashpal S Kanwar
Jun 18, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Emmanouil Chavakis, Stefanie Dimmeler
Jul 6, 2002·The Journal of Endocrinology·C J NewtonS L Atkin
Jul 9, 2002·Clinical and Experimental Pharmacology & Physiology·Dianne Z HillyardAlan G Jardine
Aug 15, 2002·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jun TangKimberly E Foreman
Jan 14, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Shiladitya SenguptaTai-Ping D Fan
Citations
Jul 22, 2005·Nature Reviews. Cancer·Jonathan PerkRobert Benezra
Feb 22, 2008·Molecular Biology of the Cell·Yi LuanChuan-Ju Liu
Nov 22, 2005·Acta Pharmacologica Sinica·Robert Wai-Sui Lim, Jin-Mei Wu
May 28, 2009·IUBMB Life·Yan FuYongzhang Luo
Apr 11, 2012·International Journal of Cancer. Journal International Du Cancer·Chenming MaWolfgang Kemmner
Nov 22, 2005·Biochemical and Biophysical Research Communications·Hong HuPeter N Kao
Apr 12, 2007·Molecular Cancer Research : MCR·Hyun-Jun KimGu Kong