PMID- 17507908
OWN - NLM
STAT- MEDLINE
DCOM- 20070921
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 72
IP  - 2
DP  - 2007 Jul
TI  - 1,25-Dihydroxyvitamin D3 targeting of NF-kappaB suppresses high glucose-induced 
      MCP-1 expression in mesangial cells.
PG  - 193-201
AB  - Macrophages accumulate in kidney glomeruli and interstitium of patients with 
      diabetic nephropathy in response to monocyte chemoattractant protein-1 (MCP-1); a 
      chemokine produced by both tubular epithelial and mesangial cells (MCs). Vitamin 
      D and its analogs have been shown to have renoprotective effects; however, there 
      are few studies involving diabetic nephropathy. We explored mechanisms by which 
      1,25-dihydroxyvitamin D3 (1,25(OH)2D3) can be renoprotective by measuring MCP-1 
      expression in MCs. Using a luciferase reporter assay, we found that high glucose 
      (HG)-induced MCP-1 transcription and that this induction is blocked by 
      1,25(OH)2D3. Electrophoretic mobility shift and chromatin immunoprecipitation 
      assays showed that HG increased the p65/p50 binding to the two NF-kappaB sites 
      within the promoter. This was suppressed by 1,25(OH)2D3, but this decrease was 
      reversed by overexpression of p65. 1,25(OH)2D3 was found to stabilize 
      IkappaBalpha leading to an inhibition of p65 translocation to the nucleus and 
      subsequent reduction of NF-kappaB binding. In primary MCs prepared from vitamin D 
      receptor knockout animals, basal MCP-1 levels were elevated but not affected by 
      1,25(OH)2D3. The analog paricalcitol inhibited the induction and activity of 
      MCP-1 while ameliorating glomerulosclerosis in streptozotocin-diabetic mice. Our 
      results suggest that 1,25(OH)2D3 might block hyperglycemia-induced renal injury 
      by blunting NF-kappaB activation.
FAU - Zhang, Z
AU  - Zhang Z
AD  - Department of Medicine and Committee on Molecular Metabolism and Nutrition, 
      Division of Biological Sciences, The University of Chicago, Chicago, Illinois 
      60637, USA.
FAU - Yuan, W
AU  - Yuan W
FAU - Sun, L
AU  - Sun L
FAU - Szeto, F L
AU  - Szeto FL
FAU - Wong, K E
AU  - Wong KE
FAU - Li, X
AU  - Li X
FAU - Kong, J
AU  - Kong J
FAU - Li, Y C
AU  - Li YC
LA  - eng
GR  - DK59327/DK/NIDDK NIH HHS/United States
GR  - DK73183/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 - 20070516
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (dihydroxy-vitamin D3)
RN  - 1406-16-2 (Vitamin D)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics
MH  - Diabetes Mellitus, Experimental
MH  - Glucose/*pharmacology
MH  - Mesangial Cells/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/*drug effects
MH  - NF-kappa B p50 Subunit/metabolism
MH  - Protein Binding/drug effects
MH  - Receptors, Calcitriol
MH  - Transcription Factor RelA/metabolism
MH  - Transcription, Genetic/*drug effects
MH  - Vitamin D/*analogs & derivatives/pharmacology
EDAT- 2007/05/18 09:00
MHDA- 2007/09/22 09:00
CRDT- 2007/05/18 09:00
PHST- 2007/05/18 09:00 [pubmed]
PHST- 2007/09/22 09:00 [medline]
PHST- 2007/05/18 09:00 [entrez]
AID - S0085-2538(15)52617-3 [pii]
AID - 10.1038/sj.ki.5002296 [doi]
PST - ppublish
SO  - Kidney Int. 2007 Jul;72(2):193-201. doi: 10.1038/sj.ki.5002296. Epub 2007 May 16.