title: 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.
authors.affiliation: Department of Biomedical Engineering, State University of New York-Stony Brook, Health Sciences Center, Stony Brook, NY, USA.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Liao
authors.forename: Irena
authors.initials: I
authors.lastname: Pastar
authors.forename: Weiliam
authors.initials: W
authors.lastname: Chen
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D012883:Skin Ulcer / Q000188:drug therapy* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D017127:Glycation End Products, Advanced; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C048496:N(6)-carboxymethyllysine; D003094:Collagen; D008239:Lysine