title: Pioglitazone inhibits the expression of matrix metalloproteinase-9, a protein involved in diabetes-associated wound healing.
abstract: Matrix metalloproteinase-9 (MMP-9) is a protein involved in diabetes-associated wound healing. The present study aimed to determine whether pioglitazone, an agonist of peroxisome proliferator-activated receptor‑γ (PPAR-γ), inhibits the expression of MMP-9. HaCaT cells at a density of 6x105 cells/well were seeded into 6-well plates in medium and were cultured for 24 h. The cells were then treated with bovine serum albumin (BSA) only or advanced glycation end‑product (AGE)-BSA (50, 100, 200, 300 or 400 µg/ml), with or without pioglitazone (0.5 or 1 µM). The effects of AGE-BSA on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of MMP-9 secreted into the medium were detected by an enzyme-linked immunosorbent assay. The mRNA and protein levels were analyzed by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. AGEs are able to increase the level of MMP-9 mRNA in HaCaT cells and the levels of MMP-9 protein secreted into the medium. Pioglitazone (0.5 or 1 µΜ) significantly inhibited the levels of MMP-9 in the treated HaCaT cells. Pioglitazone (0.5 or 1 µΜ) also suppressed the levels of MMP-9 in the cell culture medium. Pioglitazone at concentrations of 0.5 and 1 µΜ significantly suppressed the levels of MMP-9 mRNA to 20 or 8%, respectively. These results suggest that pioglitazone is able to effectively suppress the expression of MMP-9 via a transcriptional mechanism.
authors.affiliation: Department of Burns and Plastic Surgery, Changsha Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Burns and Plastic Surgery, Changsha Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Burn, Inner Mongolia Institute of Burn, Baotou Steel Hospital, Baotou, Inner Mongolia 014010, P.R. China.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048909:Diabetes Complications / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D045162:Thiazolidinediones; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D020780:Matrix Metalloproteinase 9; D000077205:Pioglitazone