Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes.
Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes.
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DOI：
10.4049/jimmunol.1502270
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发表时间：
2016-06-15
期刊：
影响因子：
--
通讯作者：
Roy S
中科院分区：
文献类型：
--
作者：
Das A;Ghatak S;Sinha M;Chaffee S;Ahmed NS;Parinandi NL;Wohleb ES;Sheridan JF;Sen CK;Roy S
乳脂球EGF因子8（MFG-E8）是一种外周糖蛋白，其作为巨噬细胞和凋亡细胞之间的桥接分子，因此在从受影响组织清除凋亡细胞中起关键作用。我们以前曾报道过，糖尿病伤口巨噬细胞的凋亡细胞清除活性或红细胞增多症是妥协。在这项工作中，我们测试了MFG-E8有助于解决炎症，支持血管生成和加速伤口闭合的假设。MFG-E8-/-小鼠表现出与炎症反应过度、血管生成和伤口闭合不良相关的细胞外红细胞增多症受损。伤口巨噬细胞衍生的MFG-E8被认为是伤口血管生成的关键驱动因素。将MFG-E8−/−骨髓移植至MFG-E8+/+小鼠导致伤口闭合受损和伤口血管化受损。另一方面，接受野生型骨髓的MFG-E8−/−小鼠表现出改善的伤口闭合和改善的伤口血管化。高血压和暴露于晚期糖化终产物使MFG-E8失活，这是使糖尿病伤口愈合复杂化的关键机制。糖尿病db/db小鼠患有受损的红细胞增多症，伴有持续的炎症和缓慢的伤口闭合。局部rMFG-E8诱导伤口炎症的消退、血管生成的改善和闭合的加速，维持了MFG-E8定向治疗剂在糖尿病伤口护理中的潜力。
Milk fat globule EGF factor 8 (MFG-E8) is a peripheral glycoprotein which acts as a bridging molecule between the macrophage and apoptotic cells thus executing a pivotal role in the scavenging of apoptotic cells from affected tissue. We have previously reported that apoptotic cell clearance activity or efferocytosis is compromised in diabetic wound macrophages. In this work we test the hypothesis that MFG-E8 helps resolve inflammation, supports angiogenesis and accelerates wound closure. MFG-E8−/− mice, displayed impaired efferocytosis associated with exaggerated inflammatory response, poor angiogenesis and wound closure. Wound macrophage-derived MFG-E8 was recognized as a critical driver of wound angiogenesis. Transplantation of MFG-E8−/− bone marrow to MFG-E8+/+ mice resulted in impaired wound closure and compromised wound vascularization. On the other hand, MFG-E8−/− mice that received wild-type bone marrow showed improved wound closure and improved wound vascularization. Hyperglycemia and exposure to advanced glycated end products inactivated MFG-E8 recognizing a key mechanism that complicates diabetic wound healing. Diabetic db/db mice suffered from impaired efferocytosis accompanied with persistent inflammation and slow wound closure. Topical rMFG-E8 induced resolution of wound inflammation, improvements in angiogenesis and acceleration of closure upholding the potential of MFG-E8 directed therapeutics in diabetic wound care.
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影响因子：
3.7
作者：
Aziz M;Jacob A;Matsuda A;Wu R;Zhou M;Dong W;Yang WL;Wang P
通讯作者：
Wang P
DOI：
10.1111/wrr.12229
发表时间：
2014-11
期刊：
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
影响因子：
--
作者：
Elgharably H;Ganesh K;Dickerson J;Khanna S;Abas M;Ghatak PD;Dixit S;Bergdall V;Roy S;Sen CK
通讯作者：
Sen CK
影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
4.8
作者：
Gordillo, Gayle M.;Biswas, Ayan;Sen, Chandan K.
通讯作者：
Sen, Chandan K.
影响因子：
6
作者：
Jacobi, J;Jang, JJ;Cooke, JP
通讯作者：
Cooke, JP