Antifibrotic effect by activation of peroxisome proliferator-activated receptor–γ in corneal fibroblasts

[摘要] Purpose: The transformation of quiescentkeratocytes to active phenotypes and the ensuing fibrotic response playimportant roles in corneal scar formation. This study aims to observethe antifibrotic effect of peroxisome proliferator-activated receptor-γ(PPARγ) agonist on corneal fibroblasts cultured in vitro, and toexplore the potential application of peroxisome proliferator-activatedreceptor agonist to the prevention of corneal opacity following woundrepair. Methods: Rabbit corneal keratocytes werecultured in a medium containing 10% serum to induce theirtransformation to fibroblasts and myofibroblasts, which are similar tothose that repair corneas. After incubation with the PPARγ agonistpioglitazone at different concentrations, the effect of pioglitazone onthe migration, contractility, and viability of corneal fibroblasts wasexamined. The secretion of matrix metalloproteinase-2 and matrixmetalloproteinase-9 was determined by gelatin zymography, and thesynthesis of collagen I and fibronectin was investigated by westernblotting. Results: Treatment with pioglitazone atconcentrations ranging from 1 to 10 μm significantly decreased cornealfibroblast migration, as determined by scrape-wound assay, inhibitedcorneal fibroblast-induced collagen lattice contraction, and reducedMMP-2 and MMP-9 secretion into the supernatant of cell cultures in adose-dependent manner. The expression of fibronectin was significantlydecreased, while the expression of collagen I was only decreased whentreated with 10 μm pioglitazone. Cell viability was not evidentlychanged compared to the control. Conclusion: This in vitro studydemonstrated the anti-fibrotic effect of pioglitazone, suggesting thatactivation of PPARγ may be a new approach for the treatment of cornealopacity and scar formation in the corneal wound healing process.

[学科分类] 生物化学/生物物理