Role of aldosterone in diabetic nephropathy

Dae-Ryong Cha, Young Sun Kang, Sang Youb Han, Yi Hwa Jee, Kum Hyun Han, Hyoung Kyu Kim, Jee Young Han, Young Sik Kim

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

In the last 10 years, many studies have focused on the non-classical action of aldosterone. One of the most important new aspects of aldosterone is its pathogenic role as proinflammatory and profibrotic molecules. It has been reported that aldosterone induces myocardial fibrosis and vascular inflammation through upregulation of various proinflammatory and profibrotic cytokines. We investigated the effect of aldosterone and spironolactone, which is a non-selective mineralocorticoid receptor antagonist, on monocyte chemoattractant peptide (MCP-1) and collagen synthesis in cultured mesangial and tubular epithelial cells. In addition, to evaluate the effect of spironolactone on diabetic nephropathy, we used Otsuka Long-Evans Tokushima Fatty (OLETF) rats which are known type 2 diabetic animal models. Spironolactone treatment did not induce any significant change in blood glucose levels and blood pressure. However, spironolactone therapy significantly inhibited urinary albumin and MCP-1 excretion. Spironolactone treatment also suppressed renal mRNA expression for MCP-1, macrophage migration inhibitory factor (MIF) as well as intrarenal protein synthesis for ED-1 and MIF. Morphologically, spironolactone treatment significantly prevented glomerulosclerosis, collagen deposition and connective tissue growth factor (CTGF) expression in diabetic rats. In cultured cell experiments, aldosterone directly increased the MCP-1, collagen secretion and spironolactone treatment abolished aldosterone-induced MCP-1 and collagen synthesis. Surprisingly, aldosterone treatment did not induce any significant change in TGFß1 gene transcription. Finally, we found that NF-kB activity was increased after stimulation with aldosterone and spironolactone therapy inhibited their activation. In addition, prior treatment with pyrrolidine dithiocarbamate (PDTC), which is a NF-KB inhibitor, inhibited aldosterone-induced MCP-1 protein secretion. These results suggest that aldosterone blockade could play a role in preventing the progression of diabetic nephropathy via anti-inflammatory and antifibrotic mechanisms.

Original languageEnglish
JournalNephrology
Volume10
Issue numberSUPPL. 2
DOIs
Publication statusPublished - 2005 Oct 1

Fingerprint

Diabetic Nephropathies
Aldosterone
Spironolactone
Collagen
Inbred OLETF Rats
Macrophage Migration-Inhibitory Factors
Mineralocorticoid Receptor Antagonists
Connective Tissue Growth Factor
NF-kappa B
Chemotactic Factors
Blood Vessels
Blood Glucose
Monocytes
Albumins
Cultured Cells
Proteins
Fibrosis
Anti-Inflammatory Agents
Up-Regulation
Animal Models

Keywords

  • Aldosterone
  • Diabetic nephropathy
  • Monocyte chemotactic peptide-1(MCP-1)
  • Spironolactone

ASJC Scopus subject areas

  • Nephrology

Cite this

Role of aldosterone in diabetic nephropathy. / Cha, Dae-Ryong; Kang, Young Sun; Han, Sang Youb; Jee, Yi Hwa; Han, Kum Hyun; Kim, Hyoung Kyu; Han, Jee Young; Kim, Young Sik.

In: Nephrology, Vol. 10, No. SUPPL. 2, 01.10.2005.

Research output: Contribution to journalArticle

Cha, Dae-Ryong ; Kang, Young Sun ; Han, Sang Youb ; Jee, Yi Hwa ; Han, Kum Hyun ; Kim, Hyoung Kyu ; Han, Jee Young ; Kim, Young Sik. / Role of aldosterone in diabetic nephropathy. In: Nephrology. 2005 ; Vol. 10, No. SUPPL. 2.
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