PMID- 16174288
OWN - NLM
STAT- MEDLINE
DCOM- 20060117
LR  - 20131121
IS  - 1320-5358 (Print)
IS  - 1320-5358 (Linking)
VI  - 10 Suppl
DP  - 2005 Oct
TI  - Reactive oxygen species amplify glucose signalling in renal cells cultured under 
      high glucose and in diabetic kidney.
PG  - S7-10
AB  - Diabetic nephropathy is characterized by excessive accumulation of extracellular 
      matrix (ECM) in the kidney. Reactive oxygen species (ROS) play a central role in 
      the ECM synthesis and degradation in the glomeruli and tubulointerstitium leading 
      to renal fibrosis. High glucose (HG) induces cellular ROS through protein kinase 
      C (PKC)-dependent activation of NADPH oxidase and through mitochondrial 
      metabolism. ROS thus generated activate signal transduction cascade (PKC, 
      mitogen-activated protein kinases, and janus kinase/signal transducers and 
      activators of transcription) and transcription factors (nuclear factor-kappaB, 
      activated protein-1, and specificity protein-1), up-regulate transforming growth 
      factor-beta1 (TGF-beta1), angiotensin II (Ang II), monocyte chemoattractant 
      protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) gene and protein 
      expression, and promote formation of advanced glycation end-products (AGE). PKC, 
      TGF-beta1, Ang II, and AGE also induce cellular ROS and signal through ROS 
      leading to enhanced ECM synthesis. NF-kappaB-MCP-1 pathway is activated by ROS 
      and promotes monocyte recruitment and profibrotic process in the kidney. HG- and 
      TGF-beta1-induced PAI-1 up-regulation is mediated by ROS and contribute to ECM 
      accumulation via suppression of plasmin ativity. TGF-beta1-induced myofibroblast 
      transformation of renal tubular epithelial cells (epithelial-mesenchymal 
      transition) is also mediated by ROS and contribute to tubulointerstitial 
      fibrosis. In summary, ROS transduce and amplify glucose signalling in renal cells 
      under high glucose environment and play a critical role in excessive ECM 
      deposition in the diabetic kidney. A better understanding of ROS production and 
      removal will allow more effective therapeutic strategies in diabetic renal and 
      other vascular complications.
FAU - Ha, Hunjoo
AU  - Ha H
AD  - Hyonam Kidney Laboratory, Soon Chun Hyang Universtiy, Yongsan-gu, Seoul, Korea.
FAU - Lee, Hi Bahl
AU  - Lee HB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Australia
TA  - Nephrology (Carlton)
JT  - Nephrology (Carlton, Vic.)
JID - 9615568
RN  - 0 (Reactive Oxygen Species)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Diabetic Nephropathies/*metabolism/pathology
MH  - Dose-Response Relationship, Drug
MH  - Glucose/*administration & dosage/*metabolism/pharmacology
MH  - Humans
MH  - Kidney/cytology/*metabolism/pathology
MH  - Reactive Oxygen Species/*metabolism
MH  - *Signal Transduction
RF  - 48
EDAT- 2005/09/22 09:00
MHDA- 2006/01/18 09:00
CRDT- 2005/09/22 09:00
PHST- 2005/09/22 09:00 [pubmed]
PHST- 2006/01/18 09:00 [medline]
PHST- 2005/09/22 09:00 [entrez]
AID - NEP448 [pii]
AID - 10.1111/j.1440-1797.2005.00448.x [doi]
PST - ppublish
SO  - Nephrology (Carlton). 2005 Oct;10 Suppl:S7-10. doi: 
      10.1111/j.1440-1797.2005.00448.x.