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Am J Physiol Renal Physiol (March 27, 2007). doi:10.1152/ajprenal.00082.2007
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Submitted on February 15, 2007
Accepted on March 25, 2007

Epiregulin promotes proliferation and migration of renal proximal tubular cells

Shougang Zhuang1*, Yan Yan2, Rebecca A Daubert3, and Rick G Schnellmann4

1 Medicine/Renal, Brown Medical School, Providence, Rhode Island, United States
2 Surgery, Medical Univeristy of South Carolina, Charleston , South Carolina, United States
3 Pharmaceutical Sciences, Medical University of SC, Charleston, South Carolina, United States
4 Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina, United States

* To whom correspondence should be addressed. E-mail: szhuang{at}lifespan.org.

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 LY294002 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.




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