PMID- 17671379
OWN - NLM
STAT- MEDLINE
DCOM- 20071016
LR  - 20211203
IS  - 1421-9670 (Electronic)
IS  - 0250-8095 (Linking)
VI  - 27
IP  - 5
DP  - 2007
TI  - Rapamycin prevents early steps of the development of diabetic nephropathy in 
      rats.
PG  - 495-502
AB  - BACKGROUND/AIMS: Recent studies suggested the involvement of the Akt/mammalian 
      target of rapamycin (mTOR) pathway in the pathogenesis of diabetic nephropathy. 
      The effect of mTOR blockade by rapamycin in diabetic nephropathy was 
      investigated, but in vivo study of rapamycin treatment in the course of early 
      diabetes is still insufficient. This study was designed to determine the 
      therapeutic effects of rapamycin on diabetic nephropathy at an early stage. 
      METHODS: Diabetes was induced in Sprague-Dawley rats with streptozotocin, and 
      rapamycin (1 mg/kg) was administered by daily gavage for 4 weeks. Renal 
      structural changes and some factors involved in the early pathogenesis of 
      diabetic nephropathy were tested. The activation level of the Akt/mTOR pathway 
      was also determined. RESULTS: Rapamycin treatment reduced albuminuria, glomerular 
      enlargement, glomerular basement membrane thickening, renal macrophage 
      recruitment, and levels of renal mRNA expression of proliferating cell nuclear 
      antigen, transforming growth factor-beta1, vascular endothelial growth factor, 
      and monocyte chemoattractant protein-1 without change in blood glucose level and 
      blood pressure in experimental diabetic rats. In addition, treatment with 
      rapamycin also down-regulated the enhanced levels of renal p-Akt, phospho-p70S6 
      kinase, and phospho-ribosomal S6 protein in diabetic rats. CONCLUSIONS: Rapamycin 
      treatment can prevent the early renal structural changes of diabetes in 
      experimental rats, and thus halt the early steps of the development of diabetic 
      nephropathy. mTOR blockade might be beneficial for the treatment of diabetic 
      nephropathy.
CI  - 2007 S. Karger AG, Basel
FAU - Yang, Yi
AU  - Yang Y
AD  - Kidney Disease Center, The First Affiliated Hospital, College of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Wang, Jingjing
AU  - Wang J
FAU - Qin, Ling
AU  - Qin L
FAU - Shou, Zhangfei
AU  - Shou Z
FAU - Zhao, Jie
AU  - Zhao J
FAU - Wang, Huiping
AU  - Wang H
FAU - Chen, Ying
AU  - Chen Y
FAU - Chen, Jianghua
AU  - Chen J
LA  - eng
PT  - Journal Article
DEP - 20070720
PL  - Switzerland
TA  - Am J Nephrol
JT  - American journal of nephrology
JID - 8109361
RN  - 0 (Anti-Inflammatory Agents)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Albuminuria/physiopathology
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Cell Proliferation/drug effects
MH  - Diabetes Mellitus, Experimental/pathology/urine
MH  - Diabetic Nephropathies/*prevention & control
MH  - Glomerular Basement Membrane/drug effects/pathology
MH  - Hypertrophy
MH  - Kidney/drug effects/pathology
MH  - Kidney Glomerulus/drug effects/pathology
MH  - Male
MH  - Protein Kinases/drug effects/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
EDAT- 2007/08/03 09:00
MHDA- 2007/10/17 09:00
CRDT- 2007/08/03 09:00
PHST- 2007/05/16 00:00 [received]
PHST- 2007/06/20 00:00 [accepted]
PHST- 2007/08/03 09:00 [pubmed]
PHST- 2007/10/17 09:00 [medline]
PHST- 2007/08/03 09:00 [entrez]
AID - 000106782 [pii]
AID - 10.1159/000106782 [doi]
PST - ppublish
SO  - Am J Nephrol. 2007;27(5):495-502. doi: 10.1159/000106782. Epub 2007 Jul 20.