Molecular medicine reports

Pioglitazone inhibits the expression of matrix metalloproteinase-9, a protein involved in diabetes-associated wound healing.

PMID 24890117


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 6x105xa0cells/well were seeded into 6-well plates in medium and were cultured for 24xa0h. The cells were then treated with bovine serum albumin (BSA) only or advanced glycation end‑product (AGE)-BSA (50, 100, 200, 300 or 400xa0µg/ml), with or without pioglitazone (0.5 or 1xa0µM). 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 1xa0µΜ) significantly inhibited the levels of MMP-9 in the treated HaCaT cells. Pioglitazone (0.5 or 1xa0µΜ) also suppressed the levels of MMP-9 in the cell culture medium. Pioglitazone at concentrations of 0.5 and 1xa0µΜ 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.