EFFECT OF HIGH-GLUCOSE CONCENTRATIONS ON THE EXPRESSION OF COLLAGENS AND FIBRONECTIN BY FIBROBLASTS IN CULTURE

Extracellular matrix macromolecules such as collagen and fibronectin a re progressively altered during aging and age-related diseases like di abetes. We investigated the effect of high-glucose concentration (mimi cking diabetic conditions) and the influence of in vitro cell aging [c omparing 4th-passage fibroblasts (P4) to 15th-passage fibroblasts (P15 )] on collagen and fibronectin synthesis. Fibroblasts were incubated a t postconfluency with radiolabeled precursors, [H-3] proline for colla gen, [S-35] methionine for fibronectin. We report that in control cond itions (5 mM glucose) collagen III production increased with in vitro cell aging. High glucose concentrations (10 and 15 mM) increased speci fically collagen III synthesis both at the mRNA and protein levels, wi thout alteration of collagen I production in P4 and P15 cells. Fibrone ctin synthesis was also increased both during in vitro cell aging and in high glucose-treated P4 fibroblasts. Taken together, these data sug gest similarities between changes of phenotypic expression of collagen and fibronectin induced by in vitro cell aging and conditions imitati ng diabetes. (C) 1998 Elsevier Science Inc.