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10.14814/phy2.13203

http://scihub22266oqcxt.onion/10.14814/phy2.13203
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28420760!5408278!28420760
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suck abstract from ncbi


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pmid28420760      Physiol+Rep 2017 ; 5 (8): ä
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  • Novel lnc RNA regulated by HIF-1 inhibits apoptotic cell death in the renal tubular epithelial cells under hypoxia #MMPMID28420760
  • Mimura I; Hirakawa Y; Kanki Y; Kushida N; Nakaki R; Suzuki Y; Tanaka T; Aburatani H; Nangaku M
  • Physiol Rep 2017[Apr]; 5 (8): ä PMID28420760show ga
  • Chronic tubulointerstitial hypoxia plays an important role as the final common pathway to end-stage renal disease. HIF-1 (hypoxia-inducible factor-1) is a master transcriptional factor under hypoxia, regulating downstream target genes. Genome-wide analysis of HIF-1 binding sites using high-throughput sequencers has clarified various kinds of downstream targets and made it possible to demonstrate the novel roles of HIF-1. Our aim of this study is to identify novel HIF-1 downstream epigenetic targets which may play important roles in the kidney. Immortalized tubular cell lines (HK2; human kidney-2) and primary cultured cells (RPTEC; renal proximal tubular cell lines) were exposed to 1% hypoxia for 24-72 h. We performed RNA-seq to clarify the expression of mRNA and long non-coding RNA (lncRNA). We also examined ChIP-seq to identify HIF-1 binding sites under hypoxia. RNA-seq identified 44 lncRNAs which are up-regulated under hypoxic condition in both cells. ChIP-seq analysis demonstrated that HIF-1 also binds to the lncRNAs under hypoxia. The expression of novel lncRNA, DARS-AS1 (aspartyl-tRNA synthetase anti-sense 1), is up-regulated only under hypoxia and HIF-1 binds to its promoter region, which includes two hypoxia-responsive elements. Its expression is also up-regulated with cobalt chloride exposure, while it is not under hypoxia when HIF-1 is knocked down by siRNA To clarify the biological roles of DARS-AS1, we measured the activity of caspase 3/7 using anti-sense oligo of DARS-AS1. Knockdown of DARS-AS1 deteriorated apoptotic cell death. In conclusion, we identified the novel lncRNAs regulated by HIF-1 under hypoxia and clarified that DARS-AS1 plays an important role in inhibiting apoptotic cell death in renal tubular cells.
  • |*Apoptosis[MESH]
  • |Cell Hypoxia[MESH]
  • |Cell Line[MESH]
  • |Epigenesis, Genetic[MESH]
  • |Epithelial Cells/*metabolism[MESH]
  • |Humans[MESH]
  • |Hypoxia-Inducible Factor 1/*metabolism[MESH]
  • |Kidney Tubules/cytology[MESH]
  • |Protein Binding[MESH]
  • |RNA, Long Noncoding/*genetics/metabolism[MESH]
  • |Response Elements[MESH]


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