Dependence of resolvin-induced increases in corneal epithelial cell migration on EGF receptor transactivation.

Abstract:

PURPOSE:To determine whether resolvin E1 (RvE1), an endogenous oxygenation product of eicosapentaenoic acid (EPA), induces increases in migration in human corneal epithelial cells (HCECs) and to identify signal pathways mediating this response. METHODS:Migration was measured with the scratch wound assay. Western blot analysis identified changes in the phosphorylation status of prospective intracellular signal transduction mediators. Immunocytochemistry probed for intracellular paxillin localization and actin reorganization. RESULTS:RvE1 enhanced HCEC migratory rates to levels comparable to those induced by epidermal growth factor (EGF). These increases were accompanied by increases in the phosphorylation status of epidermal growth factor receptor (EGFR), Akt, p38 MAPK, GSK-3α/β, and paxillin, which essentially persisted for up to 60 minutes. The EGFR inhibitor AG1478 blocked the subsequent effects of RvE1 to induce increases in phosphorylation status and cell migration. The PI3-K inhibitor LY294002 or wortmannin or the p38 inhibitor BIRB796 blocked resolvin-induced increases in cell migration. Either the matrix metalloproteinase (MMP) inhibitor GM6001 or the specific heparin-bound EGF-like growth factor inhibitor CRM197 suppressed RvE1-induced stimulation of EGFR/PI3-K/Akt phosphorylation and cell migration. CONCLUSIONS:RvE1 enhances HCEC migration through MMP and sheddase-mediated EGFR transactivation. This response is dependent on PI3-K and p38-linked signaling eliciting paxillin (Tyr118) phosphorylation.

authors

Zhang F,Yang H,Pan Z,Wang Z,Wolosin JM,Gjorstrup P,Reinach PS

doi

10.1167/iovs.09-4468

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

5601-9

issue

11

eissn

0146-0404

issn

1552-5783

pii

iovs.09-4468

journal_volume

51

pub_type

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