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

Zhang,Jun; Huang,Xiaoyuan; Wang,Lingfeng

doi:10.3892/mmr.2014.2277

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

Authors:
- Jun Zhang
- Xiaoyuan Huang
- Lingfeng Wang
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Affiliations: Department of Burns and Plastic Surgery, Changsha Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Burn, Inner Mongolia Institute of Burn, Baotou Steel Hospital, Baotou, Inner Mongolia 014010, P.R. China
Published online on: May 28, 2014 https://doi.org/10.3892/mmr.2014.2277
Pages: 1084-1088

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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.

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