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.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
July 2007
Objectives: Acyclic retinoid (ACR) is a synthetic retinoid with a high safety profile that has been pursued with high expectations for therapeutic use in prevention (recurrence) and treatment of malignancies. With the objective of addressing the therapeutic potential in the cardiovasculature, namely neointima formation, effects of ACR on neointima formation and the involved mechanisms were investigated.
Methods And Results: ACR was administered to cuff-injured mice which showed inhibition of neointima formation.
Krüppel-like factor 5 (KLF5) is a transcription factor important in regulation of the cardiovascular response to external stress. KLF5 regulates pathological cell growth, and its acetylation is important for this effect. Its mechanisms of action, however, are still unclear.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2006
Protein profiling would aid in better understanding the pathophysiology of metabolic disease. Here, we report on differential proteomic analysis using an animal model of diabetes mellitus and associated metabolic disorders (Otsuka Long-Evans Tokushima Fatty rat). Serum was analyzed by a new two-dimensional liquid chromatography system which separated proteins by chromatofocusing and subsequent reversed-phase chromatography.
View Article and Find Full Text PDFVancomycin, an antibiotic to which methicillin-resistant Staphylococcus aureus (MRSA) is sensitive, frequently induces hypersensitivity reactions. Lowering the vancomycin infusion rate and/or premedicating with antihistamine effectively reduce hypersensitivity in most cases. However, vancomycin desensitization is sometimes the only way to ensure safe use.
View Article and Find Full Text PDFThe transcription factor Krüppel-like factor 5 (KLF5) and its genetically downstream target gene platelet-derived growth factor-A (PDGF-A) chain are key factors in regulation of cardiovascular remodeling in response to stress. We show that KLF5 mediates a novel distinct delayed persistent induction of PDGF-A chain in response to the model agonist, phorbol ester, through a cis-element previously shown to mediate phorbol ester induction on to PDGF-A chain through the early growth response factor (Egr-1). Interestingly, the nuclear factor-kappaB (NF-kappaB) p50 subunit further cooperatively activates PDGF-A chain through protein-protein interaction with KLF5 but not Egr-1.
View Article and Find Full Text PDF