Endothelin a receptor blockade influences apoptosis and cellular proliferation in the developing rat kidney

Kee Hwan Yoo, Hyung Eun Yim, Gi Young Jang, In Sun Bae, Byung Min Choi, Young Sook Hong, Joo Won Lee

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Endothelin systems are believed to play important roles in the emergence and maintenance of functions of various organs during perinatal development, including the kidney. The present study was designed to investigate the roles of endothelin systems on physiologic renal growth and development. Newborn rat pups were treated with either Bristol-Myers Squibb-182874 (30 mg/kg/day), a selective endothelin A receptor (ETAR) antagonist, or vehicle for 7 days. To identify cellular changes, kidneys were examined for apoptotic cells by terminal deoxynucleotide transferasemediated nick-end labeling stain and proliferating cell nuclear antigen (PCNA) by immunohistochemical (IHC) stain. To clarify the molecular control of these processes, immunoblots and reverse transcriptase-polymerase chain reaction for Clusterin, Bcl-2, Bcl-XL, Bax, and p53 were performed. ETAR antagonist treatment resulted in reduced kidney weights, decreased PCNA-positive proliferating cells, and increased apoptotic cells. The protein expressions of renal Bcl-XL and Bax in the ETAR antagonist-treated group were significantly decreased, whereas the mRNA expressions of these genes were not changed. There were no significant differences in the expressions of Clusterin, Bcl-2, and p53. In conclusion, inhibition of endogenous endothelins impairs renal growth, in which decreased cellular proliferation, increased apoptosis and decreased expressions of renal Bcl-XL and Bax are possibly implicated.

Original languageEnglish
Pages (from-to)138-145
Number of pages8
JournalJournal of Korean medical science
Volume24
Issue number1
DOIs
Publication statusPublished - 2009 Feb

Keywords

  • Apoptosis
  • Bax
  • Bcl-2
  • Bcl-XL
  • Cell proliferation
  • Clusterin
  • Endothelins
  • Growth and development
  • Kidney
  • P53

ASJC Scopus subject areas

  • Medicine(all)

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