Effect of high-glucose concentrations on the expression of collagens and fibronectin by fibroblasts in culture.

Extracellular matrix macromolecules such as collagen and fibronectin are progressively altered during aging and age-related diseases like diabetes. We investigated the effect of high-glucose concentration (mimicking diabetic conditions) and the influence of in vitro cell aging [comparing 4th-passage fibroblasts (P4) to 15th-passage fibroblasts (P15)] on collagen and fibronectin synthesis. Fibroblasts were incubated at postconfluency with radiolabeled precursors, [3H] proline for collagen, [35S] methionine for fibronectin. We report that in control conditions (5 mM glucose) collagen III production increased with in vitro cell aging. High glucose concentrations (10 and 15 mM) increased specifically collagen III synthesis both at the mRNA and protein levels, without alteration of collagen I production in P4 and P15 cells. Fibronectin synthesis was also increased both during in vitro cell aging and in high glucose-treated P4 fibroblasts. Taken together, these data suggest similarities between changes of phenotypic expression of collagen and fibronectin induced by in vitro cell aging and conditions imitating diabetes.