Gangliosides in Diabetic Wound Healing.
Gangliosides in Diabetic Wound Healing.
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DOI：
10.1016/bs.pmbts.2017.12.006
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发表时间：
2018
影响因子：
--
通讯作者：
Paller AS
中科院分区：
文献类型：
--
作者：
Dam DHM;Paller AS
正常的皮肤伤口愈合需要一系列复杂的生物和分子现象。这些过程依赖于细胞对细胞因子、生长因子和其他介质（如凝血因子、胡萝卜素、自由基和一氧化氮）的正常细胞反应。在糖尿病性溃疡中，对这些分子的反应受损导致伤口的血管形成、神经支配、基质重建和上皮再形成的异常。角质形成细胞在细胞外基质上的迁移和增殖在上皮再形成中是关键的，但是在糖尿病中对生长因子（包括胰岛素/IGF-1信号传导轴）的反应是迟钝的。神经节苷脂GM 3是一种唾液酸化的表皮鞘糖脂，已被鉴定为抑制胰岛素/IGF-1信号传导的关键介质，其响应于诸如肿瘤坏死因子-α（TNF-α）和高血糖症的因子。GM 3和其合成所需的酶GM 3合酶（GM 3S）的表达降低导致胰岛素/IGF-1受体信号传导增加和角质形成细胞迁移加速，即使在高葡萄糖水平存在下也是如此。在GM 3S敲除糖尿病小鼠和用纳米构建体介导的GM 3S靶向基因调控局部治疗的饮食诱导的糖尿病小鼠中的GM 3消耗也加速伤口愈合。这些最近的观察结果，再加上证据表明，GM 3消耗逆转糖尿病小鼠远端神经支配异常，表明GM 3消耗策略是一个有前途的新方法，为人类糖尿病伤口。
An organized series of complicated biological and molecular phenomena is required for normal skin wound healing. These processes depend on normal cellular responses to cytokines, growth factors, and other mediators, such as clotting factors, prostaglandins, free radicals, and nitric oxide. In diabetic ulcers, impaired responses to these molecules lead to abnormalities in vascularization, innervation, matrix reconstruction, and reepithelialization of wounds. keratinocyte migration and proliferation on an extracellular matrix is critical in reepithelialization, but the response to growth factors is blunted in diabetes, including the insulin/IGF–1 signaling axis. Ganglioside GM3, a sialylated epidermal glycosphingolipid, has been identified as a key mediator of the inhibition of insulin/IGF–1 signaling in response to factors, such as tumor necrosis factor-alpha (TNF–α) and hyperglycemia. Decreased expression of GM3 and the enzyme required for its synthesis, GM3 synthase (GM3S), leads to increased insulin/IGF-1 receptor signaling and accelerated keratinocyte migration, even in the presence of high glucose levels. GM3 depletion in GM3S knockout diabetic mice and diet-induced diabetic mice treated topically with nanoconstruct-mediated GM3S-targeting gene regulation also accelerates wound healing. These recent observations, coupled with evidence that GM3 depletion reverses distal innervation abnormalities in diabetic mice, suggest that GM3-depleting strategies are a promising new approach for human diabetic wounds.
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影响因子：
3.4
作者：
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2.2
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158.5
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通讯作者：
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影响因子：
6.6
作者：
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通讯作者：
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