ACE inhibitors attenuate expression of renal transforming growth factor-β1 in humans

Gyu Tae Shin, Seung Jung Kim, Kyoung Ai Ma, Heung Soo Kim, Dohun Kim

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Progressive nephropathies are characterized by the enhanced accumulation of extracellular matrix in the kidney. Overproduction of transforming growth factor-β (TGF-β) was shown to result in pathological tissue fibrosis through the accumulation of extracellular matrix proteins. It has been proposed that angiotensin II stimulates TGF-β production. Despite accumulating data supporting the effects of angiotensin-converting enzyme (ACE) inhibitors on the attenuation of TGF-β in vitro and in rats, such studies in humans are lacking. The present study sought to determine the effects of ACE inhibitors on TGF-β1 in patients with glomerulonephritis. Using competitive polymerase chain reaction and the sandwich enzyme-linked immunosorbent assay, TGF-β1 messenger RNA (mRNA) abundance and TGF-β1 protein levels were measured. Patients with immunoglobulin A nephropathy administered ACE inhibitors showed significantly lower renal TGF-β1 gene expression than patients not administered these medications (mean ratios of TGF-β1/β-actin, 4.27 ± 0.62 [SEM] versus 14.81 ± 3.87; P < 0.05), whereas no difference was noted between patients administered ACE inhibitors and healthy controls (4.27 ± 0.62 versus 2.78 ± 0.71). ACE inhibitor therapy did not affect TGF-β1 mRNA expression in freshly isolated mononuclear cells. Urine and serum TGF-β1 protein levels were not affected by the administration of ACE inhibitors. However, possibly a longer duration of treatment would decrease TGF-β1 levels in urine or blood. In conclusion, we observed a significant reduction in TGF-β1 expression in the kidney by ACE inhibitors, and this suggests that the effects of ACE inhibitors observed in animals can be extrapolated to patients with chronic renal disease. (C) 2000 by the National Kidney Foundation, Inc.

Original languageEnglish
Pages (from-to)894-902
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume36
Issue number5
DOIs
StatePublished - 2000

Keywords

  • Angiotensin-converting enzyme (ACE) inhibitors
  • Glomerulonephritis
  • Transforming growth factor-β (TGF-β)

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