Collagen Glycation Promotes Myofibroblast Differentiation and Migration

Diabetes mellitus is a high prevalence metabolic disease that is associated with dysfunction of multiple organs including the myocardium and periodontium. Objective: As the organization, structural properties and turnover of collagen in the myocardium are markedly dysregulated by the increased glucose metabolites of diabetes, we investigated the effect of glycation on remodeling of collagen by cardiac fibroblasts. Methods: Collagen glycation was induced by the diabetes metabolite, methylglyoxal (MGO). Results: In tractional remodeling of floating and stress-relaxed collagen gels, MGO promoted faster contraction (p<0.025) than vehicle controls that was MGO dose-dependent. Cells cultured on MGO-treated collagen showed increased expression of a-smooth muscle actin but decreased focal adhesion formation compared to controls, effects that were MGO dose-dependent. Scratch and Transwell assays showed that fibroblasts migrated on MGO-treated collagen faster than controls (p<0.03). Shear assay results show that fibroblasts are less adherent on MGO-treated collagen. It was also found that MGO treatment of collagen decreased integrin activation, which we speculate allows faster migration. Conclusion: We thereby conclude that MGO promotes tractional remodeling of collagen by enhancing the formation and migration of myofibroblasts, critical processes in the maintenance of extracellular matrix homeostasis that when disrupted can affect cardiac function.