PMID- 19474189
OWN - NLM
STAT- MEDLINE
DCOM- 20090908
LR  - 20211203
IS  - 1522-1466 (Electronic)
IS  - 0363-6127 (Print)
IS  - 1522-1466 (Linking)
VI  - 297
IP  - 3
DP  - 2009 Sep
TI  - S6 kinase 1 knockout inhibits uninephrectomy- or diabetes-induced renal 
      hypertrophy.
PG  - F585-93
LID - 10.1152/ajprenal.00186.2009 [doi]
AB  - Removal of one kidney stimulates synthesis of RNA and protein, with minimal DNA 
      replication, in all nephron segments of the remaining kidney, resulting in cell 
      growth (increase in cell size) with minimal cell proliferation (increase in cell 
      number). In addition to the compensatory renal hypertrophy caused by nephron 
      loss, pathophysiological renal hypertrophy can occur as a consequence of early 
      uncontrolled diabetes. However, the molecular mechanism underlying renal 
      hypertrophy in these conditions remains unclear. In the present study, we report 
      that deletion of S6 kinase 1 (S6K1) inhibited renal hypertrophy seen following 
      either contralateral nephrectomy or induction of diabetes. In wild-type mice, 
      hypertrophic stimuli increased phosphorylation of 40S ribosomal protein S6 
      (rpS6), a known target of S6K1. Immunoblotting analysis revealed that S6K1(-/-) 
      mice exhibited moderately elevated basal levels of rpS6, which did not increase 
      further in response to the hypertrophic stimuli. Northern blotting indicated a 
      moderate upregulation of S6K2 expression in the kidneys of S6K1(-/-) mice. 
      Phosphorylation of the eukaryotic translation initiation factor 4E-binding 
      protein 1, another downstream target of the mammalian target of rapamycin (mTOR), 
      was stimulated to equivalent levels in S6K1(-/-) and S6K1(+/+) littermates during 
      renal hypertrophy, indicating that mTOR was still activated in the S6K1(-/-) 
      mice. The highly selective mTOR inhibitor, rapamycin, inhibited increased 
      phosphorylation of rpS6 and blocked 60-70% of the hypertrophy seen in wild-type 
      mice but failed to prevent the approximately 10% hypertrophy seen in S6K1(-/-) 
      mice in response to uninephrectomy (UNX) although it did inhibit the basal rpS6 
      phosphorylation. Thus the present study provides the first genetic evidence that 
      S6K1 plays a major role in the development of compensatory renal hypertrophy as 
      well as diabetic renal hypertrophy and indicates that UNX- and diabetes-mediated 
      mTOR activation can selectively activate S6K1 without activating S6K2.
FAU - Chen, Jian-Kang
AU  - Chen JK
FAU - Chen, Jianchun
AU  - Chen J
FAU - Thomas, George
AU  - Thomas G
FAU - Kozma, Sara C
AU  - Kozma SC
FAU - Harris, Raymond C
AU  - Harris RC
LA  - eng
GR  - DK51265/DK/NIDDK NIH HHS/United States
GR  - 2P60DK020593/DK/NIDDK NIH HHS/United States
GR  - P01 DK038226/DK/NIDDK NIH HHS/United States
GR  - DK078019/DK/NIDDK NIH HHS/United States
GR  - DK62794/DK/NIDDK NIH HHS/United States
GR  - DK73802/DK/NIDDK NIH HHS/United States
PT  - Editorial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090527
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Blood Glucose)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Eif4ebp1 protein, mouse)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Phosphoproteins)
RN  - 0 (Ribosomal Protein S6)
RN  - 0 (ribosomal protein S6, mouse)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Am J Physiol Renal Physiol. 2009 Sep;297(3):F583-4. PMID: 19570879
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Carrier Proteins/antagonists & inhibitors/metabolism
MH  - Cell Cycle Proteins
MH  - Cell Proliferation
MH  - Diabetes Mellitus, Experimental/*complications/enzymology
MH  - Diabetic Nephropathies/enzymology/etiology/pathology/*prevention & control
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/pharmacology
MH  - Eukaryotic Initiation Factors
MH  - Gene Expression Regulation, Enzymologic
MH  - Hypertrophy
MH  - Kidney/drug effects/*enzymology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Nephrectomy/adverse effects
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/metabolism
MH  - Ribosomal Protein S6/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*deficiency/genetics
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Time Factors
PMC - PMC2739710
EDAT- 2009/05/29 09:00
MHDA- 2009/09/09 06:00
PMCR- 2010/09/01
CRDT- 2009/05/29 09:00
PHST- 2009/05/29 09:00 [entrez]
PHST- 2009/05/29 09:00 [pubmed]
PHST- 2009/09/09 06:00 [medline]
PHST- 2010/09/01 00:00 [pmc-release]
AID - 00186.2009 [pii]
AID - F-00186-2009 [pii]
AID - 10.1152/ajprenal.00186.2009 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2009 Sep;297(3):F585-93. doi: 
      10.1152/ajprenal.00186.2009. Epub 2009 May 27.