Protein kinases C-gamma and -delta are involved in insulin-like growth factor I-induced migration of colonic epithelial cells

Background & Aims: The mechanisms by which epithelial cells migrate during the repair of damaged colonic mucosa are poorly understood. This study inve stigated the insulin-like growth factor I (IGF-I) signaling pathway leading to HT29-D4 human colonic epithelial cell line migration, Methods: IGF-stim ulated cell migration was determined using a wound model in the presence or absence of kinase inhibitors. Activation of protein kinase C (PKC) was det ermined by immunodetection, Results: IGF-I and insulin induce cell migratio n without affecting cell proliferation through their cognate receptors. Des (1-3)-IGF-I, a truncated analogue of IGF-I, was more potent than IGF-I, sug gesting that IGF-binding proteins secreted in the medium modulated IGF-I-in duced cell migration, Inhibition of phosphatidylinositol 3-kinase, PKC, and mitogen-activated protein kinases eliminated cell restitution. Long-term e xposure of cells to phorbol myristate acetate caused the depletion of PKC-d elta and -gamma and prevented also IGF-I-induced cell motility, IGF-I also induced activation of PKC-delta and -gamma only. Conclusions: IGF-I stimula tes colonic restitution through the activation of multiple signaling pathwa ys including activation of phosphatidylinositol 3-kinase, PKC-delta and -ga mma, and mitogen-activated protein kinases.