國家衛生研究院 NHRI:Item 3990099045/6962
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    题名: Krüppel-like factor 10 upregulates the expression of cyclooxygenase 1 and further modulates angiogenesis in endothelial cell and platelet aggregation in gene-deficient mice
    作者: Yang, DHA;Hsu, CF;Lin, CY;Guo, JY;Yu, WCY;Chang, VHS
    贡献者: National Institute of Cancer Research
    摘要: Krüppel-like family is a group of zinc-finger transcription factors which play key regulatory roles in cellular growth, development, differentiation and vascularization. Recent studies have shown that one of the members, KLF10, is specifically involved in the process of angiogenesis by acting as a key transcriptional regulator of TGF-β1 in pro-angiogenic cells differentiation and function. KLF10−/− mice also displayed impaired blood flow recovery after hindlimb ischemia. However, the mechanism of KLF10 induced angiogenesis is still not well understood. From ChIP-chip, which have been adopt to elucidate the novel target genes and signaling cascades of KLF10, COX-1 (also named as PTGS1) is one of the target genes that may be regulated by Klf10 through promoter binding. In order to investigate the function of KLF10/COX-1 axis, promoter activity, EMSA, ChIP-PCR and tube formation assays were serially performed. Our results demonstrated that KLF10 acts as a transcriptional activator on COX-1 promoter where overexpression of KLF10 induces COX-1 protein expression and mRNA expression in endothelial cells. It has been known that COX-1 is the key enzyme in prostaglandin biosynthesis which regulated angiogenesis in endothelial cells. Using tube formation assay, we further demonstrated that KLF10 overexpressed endothelial cells formed better organized three-dimensional tube structure in contrast to the control group did. To specifically investigate the role for KLF10 in angiogenesis, the its deficient mice exhibited decreased light transmission which represents the extend of platelet aggregation slowing down. Taken together, our results indicate an important role for KLF10 in angiogenesis through the activation of COX-1.
    日期: 2013-02
    關聯: International Journal of Biochemistry and Cell Biology. 2013 Feb;45(2):419-428.
    Link to: http://dx.doi.org/10.1016/j.biocel.2012.11.007
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1357-2725&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000315251500025
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84872354657
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