Importance of Functional EGF Receptors in Recovery from Acute Nephrotoxic Injury

Zoufei Wang, Jian Kang Chen, Su Wan Wang, Gilbert Moeckel, Raymond C. Harris

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Previous studies have demonstrated increased renal expression of EGF receptor (EGFR) and EGFR ligands in response to acute toxic or ischemic renal tubular injury and have indicated that exogenous administration of EGF accelerates recovery from such injury. However, no studies to date have proved definitively an essential role for EGFR-mediated responses in regeneration after tubule injury. To this end, waved-2 (wa-2) mice, which contain a point mutation in EGFR that reduces receptor tyrosine kinase activity by <90%, were studied. These mice have a mild phenotype (wavy coat, curly whiskers, and runted stature) and normally developed kidneys. Acute nephrotoxic injury was induced in wa-2 and wild-type mice with HgCl2. One day after HgCl2 injection, functional renal compromise was comparable in wild-type and wa-2 mice. However, the rates of recovery of serum blood urea nitrogen and creatinine levels were markedly slower in wa-2 mice. Histologic evidence of tubular injury also was more severe and persisted longer in wa-2 mice. Furthermore, their kidneys demonstrated reduced levels of DNA synthesis and increased TdT-mediated dUTP nick-end labeling staining. These studies indicate that functional EGFR activity is an essential component of the kidney's ability to recover from acute injury and that EGFR may regulate genes involved in growth, repair, and cell survival in the kidney.

Original languageEnglish (US)
Pages (from-to)3147-3154
Number of pages8
JournalJournal of the American Society of Nephrology
Volume14
Issue number12
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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