PMID- 15280531
OWN - NLM
STAT- MEDLINE
DCOM- 20050113
LR  - 20151119
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 19
IP  - 10
DP  - 2004 Oct
TI  - NF-kappaB activation and overexpression of regulated genes in human diabetic 
      nephropathy.
PG  - 2505-12
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) regulates genes involved in renal 
      disease progression, such as the chemokines monocyte chemoattractant protein-1 
      (MCP-1) and RANTES. NF-kappaB is activated in experimental models of renal 
      injury, and in vitro studies also suggest that proteinuria and angiotensin II 
      could be important NF-kappaB activators. It has been proposed that locally 
      produced MCP-1 may be involved in the development of diabetic nephropathy (DN). 
      We examined the hypothesis that NF-kappaB could be an indicator of renal damage 
      progression in DN. METHODS: Biopsy specimens from 11 patients with type 2 
      diabeties and overt nephropathy were studied by southwestern histochemistry for 
      the in situ detection of activated NF-kappaB. In addition, by 
      immunohistochemistry and/or in situ hybridization, we studied the expression of 
      MCP-1 and RANTES, whose genes are regulated by NF-kappaB. RESULTS: NF-kappaB was 
      detected mainly in cortical tubular epithelial cells and, to a lesser extent, in 
      some glomerular and interstitial cells. A strong upregulation of MCP-1 and RANTES 
      was observed in all the cases, mainly in tubular cells, and there was a strong 
      correlation between the expression of these chemokines and NF-kappaB activation 
      in the same cells, as observed in serial sections (r = 0.7; P = 0.01). In 
      addition, the tubular expression of these chemokines was correlated mainly with 
      the magnitude of the proteinuria (P = 0.002) and with interstitial cell 
      infiltration (P<0.05). CONCLUSIONS: The activation of NF-kappaB and the 
      transcription of certain pro-inflammatory chemokines in tubular epithelial cells 
      are markers of progressive DN. Proteinuria might be one of the main factors 
      inducing the observed pro-inflammatory phenotype.
FAU - Mezzano, Sergio
AU  - Mezzano S
AD  - Department of Nephrology, School of Medicine, Universidad Austral Bueras 1003 2 
      P, PO Box 8-D, Valdivia, Chile. smezzano@uach.cl
FAU - Aros, Claudio
AU  - Aros C
FAU - Droguett, Alejandra
AU  - Droguett A
FAU - Burgos, M Eugenia
AU  - Burgos ME
FAU - Ardiles, Leopoldo
AU  - Ardiles L
FAU - Flores, Claudio
AU  - Flores C
FAU - Schneider, Herman
AU  - Schneider H
FAU - Ruiz-Ortega, Marta
AU  - Ruiz-Ortega M
FAU - Egido, Jesus
AU  - Egido J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040727
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 (Biomarkers)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor RelA)
SB  - IM
MH  - Adult
MH  - Biomarkers/metabolism
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemokine CCL5/genetics/*metabolism
MH  - Diabetes Mellitus, Type 2/complications
MH  - Diabetic Nephropathies/etiology/genetics/*metabolism/pathology
MH  - Disease Progression
MH  - Female
MH  - Gene Expression
MH  - Gene Expression Regulation
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Inflammation/pathology
MH  - Kidney/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - NF-kappa B/*metabolism
MH  - NF-kappa B p50 Subunit
MH  - RNA, Messenger/metabolism
MH  - Transcription Factor RelA
MH  - Up-Regulation
EDAT- 2004/07/29 05:00
MHDA- 2005/01/14 09:00
CRDT- 2004/07/29 05:00
PHST- 2004/07/29 05:00 [pubmed]
PHST- 2005/01/14 09:00 [medline]
PHST- 2004/07/29 05:00 [entrez]
AID - gfh207 [pii]
AID - 10.1093/ndt/gfh207 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2004 Oct;19(10):2505-12. doi: 10.1093/ndt/gfh207. Epub 
      2004 Jul 27.