| First Author | Qiu J | Year | 2022 |
| Journal | Lab Invest | Volume | 102 |
| Issue | 10 | Pages | 1121-1131 |
| PubMed ID | 35710596 | Mgi Jnum | J:355673 |
| Mgi Id | MGI:7751527 | Doi | 10.1038/s41374-022-00786-8 |
| Citation | Qiu J, et al. (2022) PAQR3 depletion accelerates diabetic wound healing by promoting angiogenesis through inhibiting STUB1-mediated PPARgamma degradation. Lab Invest 102(10):1121-1131 |
| abstractText | The pathogenesis of diabetic wounds is closely associated with the dysregulation of macrophage polarization. However, the underlying mechanism remains poorly understood. In this study, we aimed to investigate the potential effects of PAQR3 (progestin and adipoQ receptor 3) silencing in accelerating diabetic wound healing. We showed that PAQR3 silencing promoted skin wound healing and angiogenesis in diabetic mice, which was accompanied by enhanced M2 macrophage polarization and elevated expression of PPARgamma (peroxisome proliferator-activated receptor gamma). PAQR3 silencing also promoted M2 polarization and increased PPARgamma protein level in PMA-treated THP-1 cells. Moreover, knockdown of PAQR3 in macrophages enhanced the migration of HaCaT cells and tube formation of HUVECs. The ubiquitination of PPARgamma protein in macrophages was repressed by PAQR3 silencing. STUB1 (STIP1 homology and U-box-containing protein 1) binds with the PPARgamma protein to mediate PPARgamma ubiquitination and degradation in macrophages, which was impaired by PAQR3 silencing. The PPARgamma inhibitor, GW9662, or STUB1 overexpression abrogated the enhanced M2 macrophage polarization induced by PAQR3 silencing. Therefore, these findings demonstrates that PAQR3 silencing accelerates diabetic wound healing by promoting M2 macrophage polarization and angiogenesis, which is mediated by the inhibition of STUB1-mediated PPARgamma protein ubiquitination and degradation. |
