PMID- 29263117
OWN - NLM
STAT- MEDLINE
DCOM- 20180718
LR  - 20210109
IS  - 2051-817X (Electronic)
IS  - 2051-817X (Linking)
VI  - 5
IP  - 24
DP  - 2017 Dec
TI  - Stabilization of hypoxia inducible factor by cobalt chloride can alter renal 
      epithelial transport.
LID - 10.14814/phy2.13531 [doi]
LID - e13531
AB  - Given the importance of the transcriptional regulator hypoxia-inducible factor-1 
      (HIF-1) for adaptive hypoxia responses, we examined the effect of stabilized 
      HIF-1alpha on renal epithelial permeability and directed sodium transport. This study 
      was motivated by histological analysis of cystic kidneys showing increased 
      expression levels of HIF-1alpha and HIF-2alpha We hypothesize that compression induced 
      localized ischemia-hypoxia of normal epithelia near a cyst leads to local 
      stabilization of HIF-1alpha, leading to altered transepithelial transport that 
      encourages cyst expansion. We found that stabilized HIF-1alpha alters both 
      transcellular and paracellular transport through renal epithelial monolayers in a 
      manner consistent with secretory behavior, indicating localized ischemia-hypoxia 
      may lead to altered salt and water transport through kidney epithelial 
      monolayers. A quantity of 100 mumol/L Cobalt chloride (CoCl(2)) was used acutely 
      to stabilize HIF-1alpha in confluent cultures of mouse renal epithelia. We measured 
      increased transepithelial permeability and decreased transepithelial resistance 
      (TER) when HIF-1alpha was stabilized. Most interestingly, we measured a change in the 
      direction of sodium current, most likely corresponding to abnormal secretory 
      function, supporting our positive-feedback hypothesis.
CI  - (c) 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on 
      behalf of The Physiological Society and the American Physiological Society.
FAU - Nag, Subhra
AU  - Nag S
AD  - Department of Biology, Geology and Environmental Sciences, Cleveland State 
      University, Cleveland, Ohio.
FAU - Resnick, Andrew
AU  - Resnick A
AUID- ORCID: 0000-0002-7526-6394
AD  - Department of Biology, Geology and Environmental Sciences, Cleveland State 
      University, Cleveland, Ohio a.resnick@csuohio.edu.
AD  - Department of Physics Cleveland State University, Cleveland, Ohio.
AD  - Center for Gene Regulation in Health and Disease, Cleveland State University, 
      Cleveland, Ohio.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Physiol Rep
JT  - Physiological reports
JID - 101607800
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 3G0H8C9362 (Cobalt)
RN  - 9NEZ333N27 (Sodium)
RN  - EVS87XF13W (cobaltous chloride)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - Cells, Cultured
MH  - Cobalt/*pharmacology
MH  - Epithelial Cells/drug effects/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Kidney Diseases, Cystic/*metabolism
MH  - Mice
MH  - Sodium/metabolism
PMC - PMC5742700
OTO - NOTNLM
OT  - Cyst
OT  - electrophysiology
OT  - hypoxia
OT  - ischemia
OT  - kidney epithelia
EDAT- 2017/12/22 06:00
MHDA- 2018/07/19 06:00
PMCR- 2017/12/21
CRDT- 2017/12/22 06:00
PHST- 2017/05/31 00:00 [received]
PHST- 2017/10/27 00:00 [revised]
PHST- 2017/10/31 00:00 [accepted]
PHST- 2017/12/22 06:00 [entrez]
PHST- 2017/12/22 06:00 [pubmed]
PHST- 2018/07/19 06:00 [medline]
PHST- 2017/12/21 00:00 [pmc-release]
AID - 5/24/e13531 [pii]
AID - PHY213531 [pii]
AID - 10.14814/phy2.13531 [doi]
PST - ppublish
SO  - Physiol Rep. 2017 Dec;5(24):e13531. doi: 10.14814/phy2.13531.