Requirement of the epidermal growth factor receptor in renal epithelial cell proliferation and migration

Shougang Zhuang, Yujing Dang, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

We showed that renal proximal tubular cells (RPTC) can proliferate and migrate following plating and oxidant or mechanical injury in the absence of exogenous growth factors; however, the mechanisms of this response remain unclear. We examined whether epidermal growth factor receptor (EGFR) signaling is activated following plating and mechanical injury and mediates RPTC proliferation and migration. EGFR, Akt [a target of phosphoinositide-3-kinase (PI3K)], and ERK1/2 were activated after plating and mechanical injury, and their phosphorylation was further enhanced by addition of exogenous EGF. Inactivation of the EGFR with the selective inhibitor AG-1478 completely blocked phosphorylation of EGFR, Akt, and ERK1/2 and blocked cell proliferaticn and migration after plating and injury. Inhibition of PI3K with LY-294002 blocked Akt phosphorylation and proliferation, whereas U-0126 blocked ERK1/2 phosphorylation but had no effect on proliferation. Furthermore, p38 was phosphorylated following mechanical injury and the p38 inhibitor SB-203580 blocked p38 phosphorylation and cell migration. In contrast, neither PI3K nor ERK1/2 inhibition blocked cell migration. These results show that EGFR activation is required for RPTC proliferation and migration and that proliferation is mediated by PI3K, whereas migration is mediated by p38.

Original languageEnglish (US)
Pages (from-to)F365-F372
JournalAmerican Journal of Physiology - Renal Physiology
Volume287
Issue number3 56-3
DOIs
StatePublished - Sep 2004
Externally publishedYes

Keywords

  • Extracellular signaling-regulated kinase
  • p38
  • Phosphoinositide-3-kinase
  • Renal proximal tubular cells

ASJC Scopus subject areas

  • Physiology
  • Urology

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