| First Author | Mirza RE | Year | 2015 |
| Journal | J Pathol | Volume | 236 |
| Issue | 4 | Pages | 433-44 |
| PubMed ID | 25875529 | Mgi Jnum | J:225544 |
| Mgi Id | MGI:5693487 | Doi | 10.1002/path.4548 |
| Citation | Mirza RE, et al. (2015) Macrophage PPARgamma and impaired wound healing in type 2 diabetes. J Pathol 236(4):433-44 |
| abstractText | Macrophages undergo a transition from pro-inflammatory to healing-associated phenotypes that is critical for efficient wound healing. However, the regulation of this transition during normal and impaired healing remains to be elucidated. In our studies, the switch in macrophage phenotypes during skin wound healing was associated with up-regulation of the peroxisome proliferator-activated receptor (PPAR)gamma and its downstream targets, along with increased mitochondrial content. In the setting of diabetes, up-regulation of PPARgamma activity was impaired by sustained expression of IL-1beta in both mouse and human wounds. In addition, experiments with myeloid-specific PPARgamma knockout mice indicated that loss of PPARgamma in macrophages is sufficient to prolong wound inflammation and delay healing. Furthermore, PPARgamma agonists promoted a healing-associated macrophage phenotype both in vitro and in vivo, even in the diabetic wound environment. Importantly, topical administration of PPARgamma agonists improved healing in diabetic mice, suggesting an appealing strategy for down-regulating inflammation and improving the healing of chronic wounds. |
