PMID- 20075061
OWN - NLM
STAT- MEDLINE
DCOM- 20100325
LR  - 20220309
IS  - 1533-3450 (Electronic)
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 21
IP  - 3
DP  - 2010 Mar
TI  - Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1.
PG  - 489-97
LID - 10.1681/ASN.2009040421 [doi]
AB  - Aberrant activation of the mammalian target of rapamycin (mTOR) pathway occurs in 
      polycystic kidney disease (PKD). mTOR inhibitors, such as rapamycin, are highly 
      effective in several rodent models of PKD, but these models result from mutations 
      in genes other than Pkd1 and Pkd2, which are the primary genes responsible for 
      human autosomal dominant PKD. To address this limitation, we tested the efficacy 
      of rapamycin in a mouse model that results from conditional inactivation of Pkd1. 
      Mosaic deletion of Pkd1 resulted in PKD and replicated characteristic features of 
      human PKD including aberrant mTOR activation, epithelial proliferation and 
      apoptosis, and progressive fibrosis. Treatment with rapamycin was highly 
      effective: It reduced cyst growth, preserved renal function, inhibited epithelial 
      cell proliferation, increased apoptosis of cyst-lining cells, and inhibited 
      fibrosis. These data provide in vivo evidence that rapamycin is effective in a 
      human-orthologous mouse model of PKD.
FAU - Shillingford, Jonathan M
AU  - Shillingford JM
AD  - Department of Molecular, Cellular, and Developmental Biology, University of 
      California Santa Barbara, Santa Barbara, CA 93106-9610, USA.
FAU - Piontek, Klaus B
AU  - Piontek KB
FAU - Germino, Gregory G
AU  - Germino GG
FAU - Weimbs, Thomas
AU  - Weimbs T
LA  - eng
GR  - DK48006/DK/NIDDK NIH HHS/United States
GR  - R37 DK048006/DK/NIDDK NIH HHS/United States
GR  - R01 DK062338/DK/NIDDK NIH HHS/United States
GR  - R01 DK048006/DK/NIDDK NIH HHS/United States
GR  - DK62338/DK/NIDDK NIH HHS/United States
GR  - R01 DK078043/DK/NIDDK NIH HHS/United States
GR  - DK078043/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100114
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Intermediate Filament Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NES protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nes protein, mouse)
RN  - 0 (Nestin)
RN  - 0 (TRPP Cation Channels)
RN  - 0 (polycystic kidney disease 1 protein)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - J Am Soc Nephrol. 2010 Mar;21(3):390-1. PMID: 20133481
MH  - Animals
MH  - Apoptosis/physiology
MH  - Blood Urea Nitrogen
MH  - Cell Division/physiology
MH  - Disease Models, Animal
MH  - Fibrosis
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Intermediate Filament Proteins/genetics
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Kidney Tubules, Collecting/pathology/physiopathology
MH  - Kidney Tubules, Distal/pathology/physiopathology
MH  - Mice
MH  - Mosaicism
MH  - Nerve Tissue Proteins/genetics
MH  - Nestin
MH  - Phenotype
MH  - Polycystic Kidney Diseases/*genetics/pathology/*physiopathology
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - TRPP Cation Channels/*genetics/metabolism
PMC - PMC2831854
EDAT- 2010/01/16 06:00
MHDA- 2010/03/26 06:00
PMCR- 2011/03/01
CRDT- 2010/01/16 06:00
PHST- 2010/01/16 06:00 [entrez]
PHST- 2010/01/16 06:00 [pubmed]
PHST- 2010/03/26 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - ASN.2009040421 [pii]
AID - 2009040421 [pii]
AID - 10.1681/ASN.2009040421 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2010 Mar;21(3):489-97. doi: 10.1681/ASN.2009040421. Epub 2010 
      Jan 14.