Rosiglitazone modulates the behaviors of diabetic host-derived fibroblasts in a carboxymethyllysine-modified collagen model

Abstract

Utilizing a three-dimensional in vitro glycated collagen model, we evaluated the therapeutic effects of a peroxisome proliferator-activated receptor-γ ligand, rosiglitazone, and its potential as a topical treatment of diabetic chronic wounds. Rosiglitazone induced fibroblast migration, α-smooth muscle actin production, and transformation into myofibroblasts in the presence of advanced glycation end products. Both transforming growth factor β and peroxisome proliferator-activated receptor-γ expression were induced, while the receptor for advanced glycation end products was suppressed. Lastly, the reduced activities of matrix metalloproteinase-2 and matrix metalloproteinases-9 in the carboxymethyllysine-modified collagen matrices by rosiglitazone increases extracellular matrix deposition. Our findings identify rosiglitazone as a candidate for localized topical treatment of diabetic chronic wounds.