AT1 antagonist modulates activin-like kinase 5 and TGF-β receptor II in the developing kidney

Hyung Eun Yim, Mee Kyung Kim, In Sun Bae, Ji Hae Kim, Byung Min Choi, Kee Hwan Yoo, Young Sook Hong, Joo Won Lee

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Previous studies by our group have demonstrated that angiotensin-converting enzyme (ACE) inhibition in the developing kidney modulates transforming growth factor-β receptors. Blocking of angiotensin II (ANG II) mainly through angiotensin II type 1 receptor (AT1) has been implicated in mediating this ACE inhibition. The present study was designed to investigate the effects of an AT1 antagonist, losartan, on transforming growth factor-β1 (TGF-β1), TGF-β receptor I [TβRI, activin-like kinase (ALK)-1, ALK-5], TGF-β receptor II (TβRII), and α-smooth muscle actin (α-SMA) expression in the developing kidney. Newborn rat pups were treated with losartan (30 mg/kg per day) or normal saline for 7 days. Kidneys were removed for immunohistochemistry, reverse transcription polymerase chain reaction (PCR), and Western blotting of TGF-β1, ALK-1, ALK-5, TβRII, and α-SMA. Renal ALK-5 and TβRII protein expressions in the losartan-treated group were found to be significantly increased (P<0.05), whereas TGF-β1, ALK-1, and α-SMA protein expressions were not changed by losartan treatment. The losartan-treated group also showed significantly increased mean tubular diameter and interstitial area of the kidney (P<0.05). These results suggest that AT1 inhibition in the developing kidney impairs renal growth and development and modulates the expression of ALK-5 and TβRII.

Original languageEnglish
Pages (from-to)1377-1388
Number of pages12
JournalPediatric Nephrology
Volume21
Issue number10
DOIs
Publication statusPublished - 2006 Oct

Keywords

  • Angiotensin II type 1 receptor
  • TGF-β receptors
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

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