Sphingosine 1-phosphate accelerates wound healing in diabetic mice
Sphingosine 1-phosphate accelerates wound healing in diabetic mice
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DOI：
10.1016/j.jdermsci.2007.06.002
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发表时间：
2007-10-01
影响因子：
4.6
通讯作者：
Soma, Yoshinao
中科院分区：
文献类型：
--
作者：
Kawanabe, Takeshi;Kawakami, Tamihiro;Soma, Yoshinao
背景：血小板大量储存1-磷酸鞘氨醇(S1P)，并释放这种具有生物活性的细胞外物质。S1P通过与内皮分化基因(EDG)/S1P家族的G蛋白偶联受体相互作用而发挥细胞间介质的作用。在EDG家族S1P受体中，EDG-5(S1P2)在S1P诱导的迁移过程中受到抑制，糖尿病损害了组织修复的多个方面。研究目的：我们研究了S1P皮下注射是否能改善健康和糖尿病小鼠全层皮肤创面的温度。我们进一步确定糖尿病小鼠联合注射S1P和EDG-5(S1P2)拮抗剂是否会影响创面加热。方法：选用8~10周龄Bala/c小鼠、糖尿病db/db小鼠和Wister大鼠。在健康和糖尿病小鼠背部皮肤上制作全层创面。每天在创面床内注射10亩M或100亩M的S1P或赋形剂对照组(BSA/PBS)。每次注射后计算伤口面积。然后在糖尿病小鼠背部创面周围注射EDG-5(S1P2)拮抗剂(JTE-013)或赋形剂(DMSO)，测量创面直径。结果：注射S1P后，正常Bala/c小鼠的伤口面积与未注射S1P的对照组相比无明显缩小。与不注射S1P的小鼠相比，注射S1P可显著促进糖尿病小鼠创面加热。S1P和EDG-5(S1P2)受体拮抗剂联合应用可诱导糖尿病小鼠创面最大温度升高。组织病理学检查显示S1P可诱导大鼠和糖尿病小鼠创面新生血管。结论：S1P在糖尿病小鼠创面新生血管形成过程中明显促进创面升温。结果表明，S1P影响和维持所有负责伤口修复的关键细胞过程，并表明这种分子在治疗糖尿病伤口方面具有独特的潜力，特别是作为一种血管生成剂治疗糖尿病伤口。(C)2007年日本皮肤病研究学会。爱思唯尔爱尔兰有限公司出版。版权所有。
Background: Blood platelets store sphingosine 1-phosphate (S1P) abundantly and release this bioactive tipid extracelluarty. S1P acts as an intercellular mediator through interaction with the endothelial differentiation gene (EDG)/S1P family of G protein-coupled receptors. Of the EDG family S1P receptors, EDG-5 (S1P2) is inhibited in migration induced by S1P Diabetes impairs numerous aspects of tissue repair. Failure of wound angiogenesis is known to delay diabetic wound healing.Objectives: We examined whether S1P subcutaneous injection could improve the heating of full-thickness skin wounds in healthy and diabetic mice. We further determine if the combined S1P and EDG-5 (S1P2) antagonist injection in diabetic mice could affect wound heating. Finally, we examined the histopathological findings of the wound following S1P injection in diabetic mice.Methods: Eight- to 10-week-old BALA/c mice, diabetic db/db mice and Wister rats were used for the studies. A full-thickness wound was made on the dorsal skin of the healthy and diabetic mice. Either 10 mu M or 100 mu M of S1P or vehicle control (BSA/PBS) was injected into the wound bed every day. We calculated the wound area after each injection. EDG-5 (S1P2) antagonist (JTE-013) or vehicle (DMSO) was then injected in addition to the S1P around the dorsal wound of diabetic mice and the wound diameter was measured. Wound tissue samples were excised following injection for histopathological examination.Results: Wound area in normal BALA/c mice did not significantly decrease upon S1P injection compared to S1P-untreated controls. S1P injection atone showed significant promotion of wound heating in diabetic mice compared to no S1P treatment. The combination of S1P and EDG-5 (S1P2) receptor antagonist administration induced maximal wound heating in diabetic mice. Histopathological examination revealed that S1P induces neo-vascularization potential in rats and diabetic mice wound.Conclusions: S1P injection in diabetic mice significantly accelerated cutaneous wound heating in the neo-vascularization process. The results demonstrate that S1P affects and sustains all key cellular processes responsible for wound repair and point to a unique potential for this molecule in the therapy of diabetic wounds, particularly as an angiogenic agent in treatment of diabetic wounds.(c) 2007 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.