PMID- 26163195
OWN - NLM
STAT- MEDLINE
DCOM- 20161018
LR  - 20211203
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 31
IP  - 2
DP  - 2016 Feb
TI  - Regulation of the epithelial Na+ channel by the mTORC2/SGK1 pathway.
PG  - 200-5
LID - 10.1093/ndt/gfv270 [doi]
AB  - The epithelial Na(+) channel (ENaC) is decisive for sodium reabsorption by the 
      aldosterone-sensitive distal nephron (ASDN) of the kidney. ENaC is regulated by 
      the serum- and glucocorticoid-inducible kinase 1 (SGK1), a kinase genomically 
      upregulated by several hormones including glucocorticoids and mineralocorticoids. 
      SGK1 is activated by the serine/threonine kinase mammalian target of rapamycin 
      (mTOR) isoform mTORC2. SGK1 knockout (sgk1(-/-) mice) impairs renal Na(+) 
      retention during salt depletion. The mTOR catalytic site inhibitor, PP242, but 
      not mTORC1 inhibitor rapamycin, inhibits ENaC, decreases Na(+) flux in isolated 
      perfused tubules and induces natriuresis in wild-type mice. PP242 does not lead 
      to further impairment of Na(+) reabsorption in sgk1(-/-) mice. The mTORC2/SGK1 
      sensitive renal Na(+) retention leads to extracellular volume expansion with 
      increase of blood pressure. A SGK1 gene variant (prevalence  approximately  3-5% in Caucasians, 
       approximately  10% in Africans) predisposes to hypertension, stroke, obesity and type 2 
      diabetes. Future studies will be required to define the role of mTORC2 in the 
      regulation of further SGK1 sensitive transport proteins, such as further ion 
      channels, carriers and the Na(+)/K(+)-ATPase. Moreover, studies are required 
      disclosing the impact of mTORC2 on SGK1 sensitive disorders, such as 
      hypertension, obesity, diabetes, thrombosis, stroke, inflammation, autoimmune 
      disease, fibrosis and tumour growth.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. 
      All rights reserved.
FAU - Lang, Florian
AU  - Lang F
AD  - Department of Physiology, University of Tubingen, Tubingen, Germany.
FAU - Pearce, David
AU  - Pearce D
AD  - Division of Nephrology, Department of Medicine, University of California at San 
      Francisco, San Francisco, CA, USA.
LA  - eng
GR  - R01 DK056695/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20150709
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Epithelial Sodium Channels)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Nuclear Proteins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (serum-glucocorticoid regulated kinase)
SB  - IM
MH  - Animals
MH  - Epithelial Sodium Channels/*metabolism
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Immediate-Early Proteins/biosynthesis/*genetics
MH  - Kidney/*metabolism/pathology
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes/biosynthesis/*genetics
MH  - Nephrons/*metabolism
MH  - Nuclear Proteins
MH  - Protein Serine-Threonine Kinases/biosynthesis/*genetics
MH  - TOR Serine-Threonine Kinases/biosynthesis/*genetics
MH  - Up-Regulation/*genetics
PMC - PMC6281043
OTO - NOTNLM
OT  - aldosterone
OT  - epithelial Na+ channel ENaC
OT  - glucocorticoids
OT  - mammalian target of rapamycin mTOR
OT  - renal Na+ excretion
EDAT- 2015/07/15 06:00
MHDA- 2016/10/19 06:00
PMCR- 2017/02/01
CRDT- 2015/07/12 06:00
PHST- 2015/04/21 00:00 [received]
PHST- 2015/06/05 00:00 [accepted]
PHST- 2015/07/12 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/10/19 06:00 [medline]
PHST- 2017/02/01 00:00 [pmc-release]
AID - gfv270 [pii]
AID - 10.1093/ndt/gfv270 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2016 Feb;31(2):200-5. doi: 10.1093/ndt/gfv270. Epub 2015 
      Jul 9.