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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Am+J+Physiol+Cell+Physiol 2014 ; 307 (11): C1058-67 Nephropedia Template TP
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Neuroprotectin/protectin D1: endogenous biosynthesis and actions on diabetic macrophages in promoting wound healing and innervation impaired by diabetes #MMPMID25273880
Hong S; Tian H; Lu Y; Laborde JM; Muhale FA; Wang Q; Alapure BV; Serhan CN; Bazan NG
Am J Physiol Cell Physiol 2014[Dec]; 307 (11): C1058-67 PMID25273880show ga
Dysfunction of macrophages (M?s) in diabetic wounds impairs the healing. M?s 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 M?s and the actions of NPD1 on diabetic M? functions in diabetic wound healing. We used an excisional skin wound model of diabetic mice, M? depletion, M?s isolated from diabetic mice, and mass spectrometry-based targeted lipidomics to study the time course progression of NPD1 levels in wounds, the roles of M?s in NPD1 biosynthesis, and NPD1 action on diabetic M? inflammatory activities. We also investigated the healing, innervation, chronic inflammation, and oxidative stress in diabetic wounds treated with NPD1 or NPD1-modulated M?s from diabetic mice. Injury induced endogenous NPD1 biosynthesis in wounds, but diabetes impeded NPD1 formation. NPD1 was mainly produced by M?s. NPD1 enhanced wound healing and innervation in diabetic mice and promoted M?s functions that accelerated these processes. The underlying mechanisms for these actions of NPD1 or NPD1-modulated M?s involved 1) attenuating M? inflammatory activities and chronic inflammation and oxidative stress after acute inflammation in diabetic wound, and 2) increasing M? production of IL10 and hepatocyte growth factor. Taken together, NPD1 appears to be a M?s-produced factor that accelerates diabetic wound healing and promotes M? 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 M?s for treatment of diabetic wounds.