12-Hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor.
12-Hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor.
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DOI：
10.1084/jem.20132063
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发表时间：
2014-06-02
期刊：
影响因子：
--
通讯作者：
Yokomizo T
中科院分区：
文献类型：
--
作者：
Liu M;Saeki K;Matsunobu T;Okuno T;Koga T;Sugimoto Y;Yokoyama C;Nakamizo S;Kabashima K;Narumiya S;Shimizu T;Yokomizo T
内源性12-HHT或合成BLT2激动剂通过刺激角质形成细胞上的BLT2，诱导TNF和MMP的产生，促进表皮伤口愈合。白三烯B4 （LTB4）受体2型（BLT2）是12(S)-羟基庚十四- 5z，8E， 10e -三烯酸（12- hht）和LTB4的G蛋白偶联受体（GPCR）。尽管BLT1具有明确的促炎作用，但BLT2的体内功能仍然难以捉摸。由于小鼠BLT2在表皮角质形成细胞中高度表达，我们研究了12-HHT/BLT2轴在皮肤伤口愈合过程中的作用。12-HHT在小鼠伤口液中积累，blt2缺陷小鼠在皮肤穿孔后表现出受损的再上皮化和延迟的伤口愈合。在野生型小鼠中，阿司匹林减少了12-HHT的产生，导致伤口愈合延迟，而在blt2缺陷小鼠中，这一现象被消除。用原代角质形成细胞和角质形成细胞系进行的体外划痕实验也表明，12-HHT/BLT2轴通过产生肿瘤坏死因子α (TNF)和基质金属蛋白酶（MMPs）加速伤口愈合。合成的BLT2激动剂加速了培养细胞以及C57BL/6J和糖尿病小鼠的伤口愈合。这些结果确定了表皮角化细胞中12-HHT/BLT2轴作用的新机制，因此建议使用BLT2激动剂作为治疗药物来加速伤口愈合，特别是对于顽固性伤口，如糖尿病溃疡。
Endogenous 12-HHT, or a synthetic BLT2 agonist promotes epidermal wound closure by stimulating BLT2 on keratinocytes, inducing TNF and MMP production. Leukotriene B4 (LTB4) receptor type 2 (BLT2) is a G protein–coupled receptor (GPCR) for 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB4. Despite the well-defined proinflammatory roles of BLT1, the in vivo functions of BLT2 remain elusive. As mouse BLT2 is highly expressed in epidermal keratinocytes, we investigated the role of the 12-HHT/BLT2 axis in skin wound healing processes. 12-HHT accumulated in the wound fluid in mice, and BLT2-deficient mice exhibited impaired re-epithelialization and delayed wound closure after skin punching. Aspirin administration reduced 12-HHT production and resulted in delayed wound closure in wild-type mice, which was abrogated in BLT2-deficient mice. In vitro scratch assay using primary keratinocytes and a keratinocyte cell line also showed that the 12-HHT/BLT2 axis accelerated wound closure through the production of tumor necrosis factor α (TNF) and matrix metalloproteinases (MMPs). A synthetic BLT2 agonist accelerated wound closure in cultured cells as well as in C57BL/6J and diabetic mice. These results identify a novel mechanism underlying the action of the 12-HHT/BLT2 axis in epidermal keratinocytes and accordingly suggest the use of BLT2 agonists as therapeutic agents to accelerate wound healing, particularly for intractable wounds, such as diabetic ulcers.
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影响因子：
2.9
作者：
Fu, XB;Li, XK;Sheng, ZY
通讯作者：
Sheng, ZY
影响因子：
3.7
作者：
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通讯作者：
Serres, M
DOI：
10.1016/j.plefa.2005.05.003
发表时间：
2005-09-01
影响因子：
3
作者：
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通讯作者：
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DOI：
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发表时间：
1974-01-01
影响因子：
11.1
作者：
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通讯作者：
SAMUELSSON, B
影响因子：
3.9
作者：
Kaushal, Mandeep;Kutty, N. Gopalan;Rao, C. Mallikarjuna
通讯作者：
Rao, C. Mallikarjuna