Deletion of the epidermal growth factor receptor in renal proximal tubule epithelial cells delays recovery from acute kidney injury

Jianchun Chen, Jiankang Chen, Raymond C. Harris

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

To determine the role of epidermal growth factor receptor (EGFR) activation in renal functional and structural recovery from acute kidney injury (AKI), we generated mice with a specific EGFR deletion in the renal proximal tubule (EGFRptKO). Ischemia-reperfusion injury markedly activated EGFR in control littermate mice; however, this was inhibited in either the knockout or wild-type mice given erlotinib, a specific EGFR tyrosine kinase inhibitor. Blood urea nitrogen and serum creatinine increased to a comparable level in EGFR ptKO and control mice 24 h after reperfusion, but the subsequent rate of renal function recovery was markedly slowed in the knockout mice. Twenty-four hours after reperfusion, both the knockout and the inhibitor-treated mice had a similar degree of histologic renal injury as control mice, but at day 6 there was minimal evidence of injury in the control mice while both EGFRptKO and erlotinib-treated mice still had persistent proximal tubule dilation, epithelial simplification, and cast formation. Additionally, renal cell proliferation was delayed due to decreased ERK and Akt signaling. Thus, our studies provide both genetic and pharmacologic evidence that proximal tubule EGFR activation plays an important role in the recovery phase after acute kidney injury.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalKidney International
Volume82
Issue number1
DOIs
Publication statusPublished - Jul 1 2012
Externally publishedYes

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Keywords

  • acute kidney injury
  • epidermal growth factor
  • ischemia-reperfusion
  • proximal tubule

ASJC Scopus subject areas

  • Nephrology

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