Epiregulin promotes proliferation and migration of renal proximal tubular cells

Shougang Zhuang, Yan Yan, Rebecca A. Daubert, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Epiregulin is an epidermal growth factor (EGF) member that activates ErBB1 and ErBB4 homodimers and all possible heterodimeric ErbB complexes. Because its role in renal cell regeneration has not been investigated, we assessed the effect of exogenous epiregulin on regeneration of renal proximal tubular cells (RPTC) in primary culture. Epiregulin (10 ng/ml) was equivalent to EGF (10 ng/ml) in enhancing RPTC proliferation and migration. Epiregulin induced activation of the EGF receptor (EGFR), Akt, a downstream kinase of phosphoinositide 3-kinase (PI3K), and extracellular signaling-regulated kinase 1/2 (ERK1/2). Treatment with AG1478, a specific EGFR inhibitor, blocked phosphorylation of EGFR, Akt, ERK1/2, proliferation, and migration. Furthermore, inactivation of PI3K with LY-294002 blocked epiregulin-induced RPTC proliferation and, to a lesser extent, migration. However, blockade of ERK1/2 had no such effects. We suggest that epiregulin is a potent mitogen for renal epithelial cells and may contribute to renal regeneration through activation of EGFR and PI3/Akt pathways.

Original languageEnglish (US)
Pages (from-to)F219-F226
JournalAmerican Journal of Physiology - Renal Physiology
Volume293
Issue number1
DOIs
StatePublished - Jul 2007
Externally publishedYes

Keywords

  • Epidermal growth factor receptor
  • Phosphoinositide 3-kinase

ASJC Scopus subject areas

  • Physiology
  • Urology

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