首页 / 院系成果 / 成果详情页

KLF 15 Works as an Early Anti-Fibrotic Transcriptional Regulator in Ang II-Induced Renal Fibrosis via Down-Regulation of CTGF Expression  期刊论文  

  • 编号:
    88a29a15-2aec-416b-810d-9032f28992f5
  • 作者:
  • 语种:
    英文
  • 期刊:
    KIDNEY & BLOOD PRESSURE RESEARCH ISSN:1420-4096 2017 年 42 卷 6 期 (999 - 1012)
  • 收录:
  • 关键词:
  • 摘要:

    Background/Aims: Angiotensin II (Ang II) has been regarded as an important profibrogenic cytokine in renal fibrosis. Kruppel-like factor 15 (KLF15) has been identified as an important negative transcription factor in renal fibrosis. However, little is known about the role of KLF15 in Ang II-induced renal fibrosis. Methods: In this study, we randomized mice into a control group, Ang II group or Ang II plus losartan group. KLF15 expression was examined with real-time PCR and immunofluorescence in these groups. In vitro, KLF15 expression was examined by Western blot in rat renal fibroblasts (NRK-49F) stimulated with Ang II, and the effect of altered KLF15 expression on the regulation of the profibrotic factor connective tissue growth factor (CTGF) was further explored with co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP) analyses. Results: Compared with the control group, the murine model of Ang II-induced renal fibrosis demonstrated a significant decrease in renal KLF15 expression at 4 weeks and presented with progressive renal fibrosis at 6 weeks. Meanwhile, losartan, an angiotensin type 1 (AT1) receptor antagonist, effectively prevented the down-regulation of KLF15 expression induced by Ang II infusion. In vitro, NRK-49F cells stimulated with Ang II exhibited a significant decrease in KLF15 expression, accompanied by a marked increase in the expression of profibrotic factors and in the production of extracellular matrix. The up-regulation of CTGF expression induced by Ang II stimulation was inhibited by KLF15 overexpression in NRK-49F cells, and losartan treatment prevented the down-regulation of KLF15 expression and the up-regulation of CTGF expression induced by Ang II stimulation. Furthermore, CoIP and ChIP assays revealed that the transcription regulator KLF15 directly bound to the co-activator P/CAF and repressed its recruitment to the CTGF promoter. Conclusions: Ang II down-regulates KLF15 expression via the AT1 receptor, and KLF15 is likely to inhibit Ang II-induced CTGF expression by repressing the recruitment of the co-activator P/CAF to the CTGF promoter. (c) 2017 The Author(s) Published by S. Karger AG, Basel

  • 推荐引用方式
    GB/T 7714:
    Gu Xiangchen,Xu Dechao,Fu Lili, et al. KLF 15 Works as an Early Anti-Fibrotic Transcriptional Regulator in Ang II-Induced Renal Fibrosis via Down-Regulation of CTGF Expression [J].KIDNEY & BLOOD PRESSURE RESEARCH,2017,42(6):999-1012.
  • APA:
    Gu Xiangchen,Xu Dechao,Fu Lili,Wang Yi,&Gao Xiang.(2017).KLF 15 Works as an Early Anti-Fibrotic Transcriptional Regulator in Ang II-Induced Renal Fibrosis via Down-Regulation of CTGF Expression .KIDNEY & BLOOD PRESSURE RESEARCH,42(6):999-1012.
  • MLA:
    Gu Xiangchen, et al. "KLF 15 Works as an Early Anti-Fibrotic Transcriptional Regulator in Ang II-Induced Renal Fibrosis via Down-Regulation of CTGF Expression" .KIDNEY & BLOOD PRESSURE RESEARCH 42,6(2017):999-1012.
  • 入库时间:
    1/6/2020 6:07:53 PM
  • 更新时间:
    1/6/2020 6:07:53 PM
  • 条目包含文件:
    文件类型:PDF,文件大小:
    正在加载全文
浏览次数:53 下载次数:0
浏览次数:53
下载次数:0
打印次数:0
浏览器支持: Google Chrome   火狐   360浏览器极速模式(8.0+极速模式) 
返回顶部