Spironolactone ameliorates renal injury and connective tissue growth factor expression in type II diabetic rats

K. H. Han, Young Sun Kang, S. Y. Han, Y. H. Jee, M. H. Lee, J. Y. Han, H. K. Kim, Young Sik Kim, Dae-Ryong Cha

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Abstract

Administration of spironolactone provides a beneficial effect in various animal models of renal injury. In this study, we investigated whether spironolactone prevents the progression of diabetic nephropathy through reduction of connective tissue growth factor (CTGF) synthesis in type II diabetic rats. In addition, we evaluated the effect of aldosterone and spironolactone on CTGF and collagen production in cultured cells. Renal functional and morphologic changes were examined in Otsuka Long-Evans Tokushima Fatty rats with or without spironolactone treatment (20 mg/kg/day) for 8 months, as well as in non-diabetic age-matched Long-Evans Tokushima Otsuka rats. Spironolactone treatment did not induce any significant differences in body weight, kidney/body weight ratio, serum creatinine concentration, blood glucose levels, or systolic blood pressure. However, urinary protein and albumin excretion were significantly decreased in the spironolactone treatment group, which was associated with amelioration of glomerulosclerosis. In addition, renal CTGF, collagen synthesis demonstrated marked decreases in the spironolactone treatment group. In cultured MC and PTC, aldosterone induced significant increases in CTGF gene expression and protein synthesis associated with increased collagen synthesis, which was abolished by prior treatment with spironolactone. However, aldosterone treatment did not induce transforming growth factor (TGF)-β1 overproduction, and inhibition of TGF-β1 by neutralization of TGF-β1 protein did not significantly prevent aldosterone-induced CTGF production. These results suggest that the antifibrotic effects of spironolactone may be mediated by CTGF through a TGF-β1-independent pathway in this animal model of diabetic nephropathy.

Original languageEnglish
Pages (from-to)111-120
Number of pages10
JournalKidney International
Volume70
Issue number1
DOIs
Publication statusPublished - 2006 Jul 12

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Connective Tissue Growth Factor
Spironolactone
Kidney
Wounds and Injuries
Transforming Growth Factors
Aldosterone
Inbred OLETF Rats
Collagen
Diabetic Nephropathies
Animal Models
Body Weight
Blood Pressure
Proteins
Factor IX
Blood Glucose
Albumins
Cultured Cells
Creatinine
Gene Expression

Keywords

  • Connective tissue growth factor
  • DM nephropathy
  • Spironolactone
  • Type II diabetic rat

ASJC Scopus subject areas

  • Nephrology

Cite this

Spironolactone ameliorates renal injury and connective tissue growth factor expression in type II diabetic rats. / Han, K. H.; Kang, Young Sun; Han, S. Y.; Jee, Y. H.; Lee, M. H.; Han, J. Y.; Kim, H. K.; Kim, Young Sik; Cha, Dae-Ryong.

In: Kidney International, Vol. 70, No. 1, 12.07.2006, p. 111-120.

Research output: Contribution to journalArticle

Han, K. H. ; Kang, Young Sun ; Han, S. Y. ; Jee, Y. H. ; Lee, M. H. ; Han, J. Y. ; Kim, H. K. ; Kim, Young Sik ; Cha, Dae-Ryong. / Spironolactone ameliorates renal injury and connective tissue growth factor expression in type II diabetic rats. In: Kidney International. 2006 ; Vol. 70, No. 1. pp. 111-120.
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AB - Administration of spironolactone provides a beneficial effect in various animal models of renal injury. In this study, we investigated whether spironolactone prevents the progression of diabetic nephropathy through reduction of connective tissue growth factor (CTGF) synthesis in type II diabetic rats. In addition, we evaluated the effect of aldosterone and spironolactone on CTGF and collagen production in cultured cells. Renal functional and morphologic changes were examined in Otsuka Long-Evans Tokushima Fatty rats with or without spironolactone treatment (20 mg/kg/day) for 8 months, as well as in non-diabetic age-matched Long-Evans Tokushima Otsuka rats. Spironolactone treatment did not induce any significant differences in body weight, kidney/body weight ratio, serum creatinine concentration, blood glucose levels, or systolic blood pressure. However, urinary protein and albumin excretion were significantly decreased in the spironolactone treatment group, which was associated with amelioration of glomerulosclerosis. In addition, renal CTGF, collagen synthesis demonstrated marked decreases in the spironolactone treatment group. In cultured MC and PTC, aldosterone induced significant increases in CTGF gene expression and protein synthesis associated with increased collagen synthesis, which was abolished by prior treatment with spironolactone. However, aldosterone treatment did not induce transforming growth factor (TGF)-β1 overproduction, and inhibition of TGF-β1 by neutralization of TGF-β1 protein did not significantly prevent aldosterone-induced CTGF production. These results suggest that the antifibrotic effects of spironolactone may be mediated by CTGF through a TGF-β1-independent pathway in this animal model of diabetic nephropathy.

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