| First Author | Hong S | Year | 2014 |
| Journal | Am J Physiol Cell Physiol | Volume | 307 |
| Issue | 11 | Pages | C1058-67 |
| PubMed ID | 25273880 | Mgi Jnum | J:223587 |
| Mgi Id | MGI:5659790 | Doi | 10.1152/ajpcell.00270.2014 |
| Citation | Hong S, et al. (2014) Neuroprotectin/protectin D1: endogenous biosynthesis and actions on diabetic macrophages in promoting wound healing and innervation impaired by diabetes. Am J Physiol Cell Physiol 307(11):C1058-67 |
| abstractText | Dysfunction of macrophages (MPhis) in diabetic wounds impairs the healing. MPhis produce anti-inflammatory and pro-resolving neuroprotectin/protectin D1 (NPD1/PD1, 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid); however, little is known about endogenous NPD1 biosynthesis by MPhis and the actions of NPD1 on diabetic MPhi functions in diabetic wound healing. We used an excisional skin wound model of diabetic mice, MPhi depletion, MPhis isolated from diabetic mice, and mass spectrometry-based targeted lipidomics to study the time course progression of NPD1 levels in wounds, the roles of MPhis in NPD1 biosynthesis, and NPD1 action on diabetic MPhi inflammatory activities. We also investigated the healing, innervation, chronic inflammation, and oxidative stress in diabetic wounds treated with NPD1 or NPD1-modulated MPhis from diabetic mice. Injury induced endogenous NPD1 biosynthesis in wounds, but diabetes impeded NPD1 formation. NPD1 was mainly produced by MPhis. NPD1 enhanced wound healing and innervation in diabetic mice and promoted MPhis functions that accelerated these processes. The underlying mechanisms for these actions of NPD1 or NPD1-modulated MPhis involved 1) attenuating MPhi inflammatory activities and chronic inflammation and oxidative stress after acute inflammation in diabetic wound, and 2) increasing MPhi production of IL10 and hepatocyte growth factor. Taken together, NPD1 appears to be a MPhis-produced factor that accelerates diabetic wound healing and promotes MPhi pro-healing functions in diabetic wounds. Decreased NPD1 production in diabetic wound is associated with impaired healing. This study identifies a new molecular target that might be useful in development of more effective therapeutics based on NPD1 and syngeneic diabetic MPhis for treatment of diabetic wounds. |
