TNFα promotes mucosal wound repair through enhanced platelet activating factor receptor signaling in the epithelium
TNFα promotes mucosal wound repair through enhanced platelet activating factor receptor signaling in the epithelium
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DOI：
10.1038/s41385-019-0150-8
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发表时间：
2019-07-01
影响因子：
8
通讯作者：
Nusrat, Asma
中科院分区：
文献类型：
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作者：
Birkl, Dorothee;Quiros, Miguel;Nusrat, Asma
包括溃疡性结肠炎和克罗恩病在内的几种慢性炎性疾病的病理学与粘膜表面的间歇性自发性损伤/溃疡有关。疾病发病率与促炎细胞因子肿瘤坏死因子α（TNF α）的病理释放有关。在这份报告中，我们表明，TNF α通过上调肠上皮细胞中的GPCR血小板活化因子受体（PAFR）促进肠粘膜修复。血小板活化因子（PAF）在愈合的粘膜伤口中增加，并且其与上皮PAFR的接合导致表皮生长因子受体、Src和Rac 1信号传导的激活以促进伤口闭合。与这些发现一致，在给予中和TNF α抗体后和缺乏PAFR的小鼠中观察到结肠粘膜修复延迟。这些发现表明，在损伤的粘膜中，含有TNF α和PAF的促炎环境为PAFR信号传导介导的修复事件奠定了基础。
Pathobiology of several chronic inflammatory disorders, including ulcerative colitis and Crohn's disease is related to intermittent, spontaneous injury/ulceration of mucosal surfaces. Disease morbidity has been associated with pathologic release of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha). In this report, we show that TNF alpha promotes intestinal mucosal repair through upregulation of the GPCR platelet activating factor receptor (PAFR) in the intestinal epithelium. Platelet activating factor (PAF) was increased in healing mucosal wounds and its engagement with epithelial PAFR leads to activation of epidermal growth factor receptor, Src and Rac1 signaling to promote wound closure. Consistent with these findings, delayed colonic mucosal repair was observed after administration of a neutralizing TNF alpha antibody and in mice lacking PAFR. These findings suggest that in the injured mucosa, the pro-inflammatory milieu containing TNF alpha and PAF sets the stage for reparative events mediated by PAFR signaling.yyyy