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Publications (3)9.39 Total impact

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    ABSTRACT: Previous studies have demonstrated that both retinoids and apelin possess potent cardiovascular properties and that retinoids can mediate the expression of many genes in the cardiovascular system. However, it is not clear whether and how retinoids regulate apelin expression in rat vascular smooth muscle cells (VSMCs). In this study, we investigated the molecular mechanism of apelin expression regulation by synthetic retinoid Am80 in VSMCs. The results showed that Am80 markedly upregulated apelin mRNA and protein levels in VSMCs. Furthermore, KLF5 and Sp1 cooperatively mediated Am80-induced apelin expression through their direct binding to the TGF-β control element (TCE) on the apelin promoter. Interestingly, upon Am80 stimulation, the retinoic acid receptor alpha (RARα) was recruited to the apelin promoter by interacting with KLF5 and Sp1 prebound to the TCE site of the apelin promoter to form a transcriptional activation complex, subsequently leading to the upregulation of apelin expression in VSMCs. Thus, these results describe a novel mechanism of apelin regulation by Am80 and further expand the network of RARα in the retinoid pathway.
    Biochemical Journal 08/2013; · 4.65 Impact Factor
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    ABSTRACT: The Krüppel-like factor 4 is a DNA-binding transcriptional regulator that regulates a diverse array of cellular processes, including development, differentiation, proliferation, and apoptosis. The previous studies about KLF4 functions mainly focused on its role as a transcription factor, its functions in the cytoplasm are still unknown. In this study, we found that PDGF-BB could prompt the translocation of KLF4 to the cytoplasm through CRM1-mediated nuclear export pathway in vascular smooth muscle cells (VSMCs) and increased the interaction of KLF4 with actin in the cytoplasm. Further study showed that both KLF4 phosphorylation and SUMOylation induced by PDGF-BB participates in regulation of cytoskeletal organization by stabilizng the actin cytoskeleton in VSMCs. In conclusion, these results identify that KLF4 participates in the cytoskeletal organization by stabilizing cytoskeleton in the cytoplasm of VSMCs.
    Biochemical and Biophysical Research Communications 05/2013; · 2.41 Impact Factor
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    ABSTRACT: Krüppel-like factor 5 (KLF5) plays an important role in cellular proliferation and differentiation. In this study, we show that adenovirus-mediated overexpression of KLF5 increased neointimal formation, while human heart LIM protein (hhLIM) decreased neointimal formation following vascular injury. Interestingly, neointimal formation was significantly increased in the animals where both hhLIM and KLF5 were introduced, suggesting that KLF5 can reverse hhLIM function in cell proliferation on the coexpression with hhLIM. These results were also confirmed the cellular level. Further mechanistic studies suggested that PDGF-BB promoted the interaction between hhLIM and KLF5 through stimulating hhLIM binding to TGF-β control element (TCE) on the cyclin E promoter in a KLF5-dependent manner. Failure of KLF5 binding to the TCE, on the knockdown of KLF5 by transfecting siRNA, not only prevented the recruitment of hhLIM to the cyclin E promoter but also affected activation of the cyclin E promoter by KLF5. These data suggest that KLF5 reverses hhLIM function from anti-proliferation to pro-proliferation through its interaction with hhLIM on the cyclin E promoter.
    Molecular and Cellular Biochemistry 05/2012; 367(1-2):185-94. · 2.33 Impact Factor