PMID- 28420760
OWN - NLM
STAT- MEDLINE
DCOM- 20180201
LR  - 20210109
IS  - 2051-817X (Electronic)
IS  - 2051-817X (Linking)
VI  - 5
IP  - 8
DP  - 2017 Apr
TI  - Novel lnc RNA regulated by HIF-1 inhibits apoptotic cell death in the renal 
      tubular epithelial cells under hypoxia.
LID - 10.14814/phy2.13203 [doi]
LID - e13203
AB  - 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.
CI  - (c) 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on 
      behalf of The Physiological Society and the American Physiological Society.
FAU - Mimura, Imari
AU  - Mimura I
AD  - Division of Nephrology and Endocrinology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan.
FAU - Hirakawa, Yosuke
AU  - Hirakawa Y
AD  - Division of Nephrology and Endocrinology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan.
FAU - Kanki, Yasuharu
AU  - Kanki Y
AD  - Isotope Science Center, The University of Tokyo., Tokyo, Japan.
FAU - Kushida, Natsuki
AU  - Kushida N
AD  - Division of Nephrology and Endocrinology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan.
FAU - Nakaki, Ryo
AU  - Nakaki R
AD  - Division of GenomeScience, Research Center for Advanced Science and Technology, 
      The University of Tokyo, Tokyo, Japan.
FAU - Suzuki, Yutaka
AU  - Suzuki Y
AD  - Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Tanaka, Tetsuhiro
AU  - Tanaka T
AD  - Division of Nephrology and Endocrinology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan.
FAU - Aburatani, Hiroyuki
AU  - Aburatani H
AD  - Division of GenomeScience, Research Center for Advanced Science and Technology, 
      The University of Tokyo, Tokyo, Japan.
FAU - Nangaku, Masaomi
AU  - Nangaku M
AD  - Division of Nephrology and Endocrinology, Graduate School of Medicine, The 
      University of Tokyo, Tokyo, Japan mnangaku-tky@umin.ac.jp.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Physiol Rep
JT  - Physiological reports
JID - 101607800
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (RNA, Long Noncoding)
SB  - IM
MH  - *Apoptosis
MH  - Cell Hypoxia
MH  - Cell Line
MH  - Epigenesis, Genetic
MH  - Epithelial Cells/*metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Kidney Tubules/cytology
MH  - Protein Binding
MH  - RNA, Long Noncoding/*genetics/metabolism
MH  - Response Elements
MH  - Up-Regulation
PMC - PMC5408278
OTO - NOTNLM
OT  - Apoptosis
OT  - HIF-1
OT  - hypoxia
OT  - lncRNA
OT  - tubular cells
EDAT- 2017/04/20 06:00
MHDA- 2018/02/02 06:00
PMCR- 2017/04/18
CRDT- 2017/04/20 06:00
PHST- 2017/02/05 00:00 [received]
PHST- 2017/02/15 00:00 [accepted]
PHST- 2017/04/20 06:00 [entrez]
PHST- 2017/04/20 06:00 [pubmed]
PHST- 2018/02/02 06:00 [medline]
PHST- 2017/04/18 00:00 [pmc-release]
AID - 5/8/e13203 [pii]
AID - PHY213203 [pii]
AID - 10.14814/phy2.13203 [doi]
PST - ppublish
SO  - Physiol Rep. 2017 Apr;5(8):e13203. doi: 10.14814/phy2.13203.