Role of PPARbeta in fibroblast response to heat injury

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family of ligand-inducible transcription factors. Our previous study has shown that in human umbilical vein endothelial cells PPARbeta initiates a protective mechanism that limits the extent of damage due to H2O2-induced injury. Although fibroblasts are one of the main cell types involved in wound repair, the role of PPARbeta in the fibroblast response to heat injury has not been investigated. Thus, in this study, we examined possible protective role of PPARbeta in fibroblasts from heat injury. We developed a novel dermal fibroblast heat injury model to characterize the mechanisms of the heat injury healing response that involved PPARbeta. The specific PPARbeta ligand GW0742, a PPARbeta activator and a short hairpin RNA (shRNA) plasmid against PPARbeta were used to reveal the action mechanism of PPARbeta in heat injury-induced fibroblast changes in morphology and increased proliferation. In response to heat injury (52 degrees C for 30 s), fibroblast activation of PPARbeta increased 1.56-fold. Administration of GW0742 significantly induced a protective effect on heat injury-induced fibroblasts by minimizing the structural damage and increasing the cell proliferation response. Likewise, inhibition of PPARbeta using shRNA exacerbated the damage by inhibiting the de novo synthesis of PPARbeta. These results indicated that heat injury enhanced PPARbeta expression and PPARbeta protected fibroblast structure and proliferation.