PMID- 16571782
OWN - NLM
STAT- MEDLINE
DCOM- 20061102
LR  - 20220408
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 17
IP  - 5
DP  - 2006 May
TI  - Spironolactone prevents diabetic nephropathy through an anti-inflammatory 
      mechanism in type 2 diabetic rats.
PG  - 1362-72
AB  - Aldosterone induces myocardial fibrosis and vascular inflammation via 
      proinflammatory and profibrotic cytokines. The effect of spironolactone on renal 
      inflammation and renal function was investigated in type 2 diabetic rats. For 
      define the molecular mechanism of spironolactone, the effect of spironolactone on 
      the synthesis of monocyte chemotactic peptide-1 (MCP-1) and its upstream 
      transcription factor, NF-kappaB, was evaluated in cultured mesangial cells and 
      proximal tubular cells. There were no changes in blood glucose concentration or 
      BP after spironolactone treatment. Spironolactone treatment significantly reduced 
      urinary albumin excretion and ameliorated glomerulosclerosis. Urinary levels of 
      MCP-1 were significantly increased concurrently with renal expression of MCP-1, 
      macrophage migration inhibitory factor, and macrophage infiltration. 
      Spironolactone treatment significantly inhibited urinary excretion of MCP-1 as 
      well as renal MCP-1 and migration inhibitory factor expression and macrophage 
      infiltration. In addition, aldosterone induced upregulation of MCP-1 expression 
      and NF-kappaB transcriptional activity in cultured cells, and spironolactone 
      reduced both NF-kappaB activation and MCP-1 synthesis. Furthermore, NF-kappaB 
      inhibition abolished aldosterone-induced MCP-1 production. Overall, these 
      findings suggest that aldosterone-induced NF-kappaB activation leads to 
      activation of proinflammatory cytokines, ultimately leading to renal injury in 
      this model. These data suggest that mineralocorticoid blockade may be a potential 
      therapeutic target in diabetic nephropathy.
FAU - Han, Sang-Youb
AU  - Han SY
AD  - Department of Internal Medicine, Korea University Ansan Hospital, 516 Kojan-Dong, 
      Ansan City, Kyungki-Do 425-020, Korea.
FAU - Kim, Cy-Hyun
AU  - Kim CH
FAU - Kim, Han-Seong
AU  - Kim HS
FAU - Jee, Yi-Hwa
AU  - Jee YH
FAU - Song, Hye-Kyoung
AU  - Song HK
FAU - Lee, Mi-Hwa
AU  - Lee MH
FAU - Han, Kum-Hyun
AU  - Han KH
FAU - Kim, Hyoung-Kyu
AU  - Kim HK
FAU - Kang, Young-Sun
AU  - Kang YS
FAU - Han, Jee-Young
AU  - Han JY
FAU - Kim, Young-Sik
AU  - Kim YS
FAU - Cha, Dae-Ryong
AU  - Cha DR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060329
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 0 (NF-kappa B)
RN  - 27O7W4T232 (Spironolactone)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/administration & dosage
MH  - Cells, Cultured
MH  - Chemokine CCL2/immunology
MH  - Diabetes Mellitus, Type 2/*drug therapy/*immunology/pathology
MH  - Diabetic Nephropathies/*immunology/pathology/*prevention & control
MH  - Kidney/drug effects/*immunology/pathology
MH  - Mineralocorticoid Receptor Antagonists/administration & dosage
MH  - NF-kappa B/immunology
MH  - Rats
MH  - Spironolactone/*administration & dosage
EDAT- 2006/03/31 09:00
MHDA- 2006/11/03 09:00
CRDT- 2006/03/31 09:00
PHST- 2006/03/31 09:00 [pubmed]
PHST- 2006/11/03 09:00 [medline]
PHST- 2006/03/31 09:00 [entrez]
AID - ASN.2005111196 [pii]
AID - 10.1681/ASN.2005111196 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2006 May;17(5):1362-72. doi: 10.1681/ASN.2005111196. Epub 2006 
      Mar 29.