| First Author | Huang R | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 2150 |
| PubMed ID | 28526834 | Mgi Jnum | J:273515 |
| Mgi Id | MGI:6294168 | Doi | 10.1038/s41598-017-02095-3 |
| Citation | Huang R, et al. (2017) The Transcription Factor IRF6 Co-Represses PPARgamma-Mediated Cytoprotection in Ischemic Cerebrovascular Endothelial Cells. Sci Rep 7(1):2150 |
| abstractText | Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) in the cerebrovascular endothelium is a key suppressor of post-stroke brain damage. However, the role of PPARgamma's co-regulators during cerebral ischemia remains largely unknown. Here, we show that the transcription factor IRF6 is a novel PPARgamma co-regulator that directly binds to and suppresses PPARgamma activity in murine cerebrovascular endothelial cells. Moreover, IRF6 was also revealed to be a transcriptional target of PPARgamma suppression, with PPARgamma silencing significantly promoting IRF6 expression in cerebrovascular endothelial cells. In addition, IRF6 silencing significantly promoted pioglitazone's cytoprotective effects in ischemic murine cerebrovascular endothelial cells. Mechanistically, IRF6 significantly suppressed PPARgamma's transcriptional inhibition of the ischemia-induced, pro-apoptotic microRNA miR-106a. In conclusion, we identified IRF6 as a novel PPARgamma co-suppressor that serves a key role in suppressing PPARgamma-mediated cerebrovascular endothelial cytoprotection following ischemia. Further investigation into IRF6 and other PPARgamma co-regulators should provide additional insights into PPARgamma's cytoprotective role in the cerebrovascular endothelium following stroke. |
