Modulation of heart fibroblast migration and collagen gel contraction by IGF-I

Dynamic interactions between cells and the extracellular matrix are essenti al in the regulation of a number of cellular processes including migration, adhesion, proliferation and differentiation. A variety of factors have bee n identified which modulate these interactions including transforming growt h factor-beta, platelet-derived growth factor and others. Insulin-like grow th factors have been shown to regulate collagen production by heart fibrobl asts; however, the effects of this growth factor on the interactions of hea rt fibroblasts with the extracellular matrix have not been examined. The pr esent studies were carried out to determine the effects of IGF-I on the abi lity of fibroblasts to interact with the extracellular matrix and to begin to determine the mechanisms of this response. These experiments illustrate that IGF-I treatment results in increased migration, collagen reorganizatio n and gel contraction by heart fibroblasts. IGF-I has been shown to activat e both the mitogen-activated protein kinase and phophatidylinositol-3 kinas e pathways in isolated cells. Experiments with pharmacological antagonists of these pathways indicate that the mitogen-activated protein kinase pathwa y is essential for IGF-I stimulated collagen gel contraction by fibroblasts . These studies illustrate that IGF-I modulates the ability of fibroblasts to interact with the collagen matrix and that activation of multiple signal ing pathways by IGF-I may produce distinct downstream responses in these ce lls.