Acyclic retinoid inhibits functional interaction of transcription factors Krüppel-like factor 5 and retinoic acid receptor-alpha.
We show that transcription factor Krüppel-like factor 5 (KLF5), which is important in cardiovascular remodeling, interacts with retinoic acid receptor-alpha (RARalpha) to regulate downstream gene expression. Here, we investigated whether acyclic retinoid (ACR) regulates KLF5 and inhibits vascular remodeling. Co-immunoprecipitation and pull-down binding assay showed that ACR attenuates functional interaction of KLF5 and RARalpha. ACR affects KLF5 functions by regulating transactivation of platelet-derived growth factor A (PDGF-A) chain. ACR may be a new vascular therapy to target KLF5 in cardiovascular pathology.
Kada
Nanae
N
Departments of Cardiovascular Medicine and Ubiquitous Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Suzuki
Toru
T
Aizawa
Kenichi
K
Munemasa
Yoshiko
Y
Matsumura
Takayoshi
T
Sawaki
Daigo
D
Nagai
Ryozo
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D047468:Immunoprecipitation; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; C118391:Klf5 protein, mouse; D051741:Kruppel-Like Transcription Factors; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid