Netrin-1 promotes diabetic corneal wound healing through molecular mechanisms mediated via the adenosine 2B receptor.
Netrin-1 promotes diabetic corneal wound healing through molecular mechanisms mediated via the adenosine 2B receptor.
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Netrin-1 通过腺苷 2B 受体介导的分子机制促进糖尿病角膜伤口愈合
DOI：
10.1038/s41598-018-24506-9
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发表时间：
2018-04-16
影响因子：
4.6
通讯作者：
Gao H
中科院分区：
文献类型：
--
作者：
Zhang Y;Chen P;Di G;Qi X;Zhou Q;Gao H
Netrins是一种分泌性的化学引诱物，在轴突导向、细胞迁移和上皮可塑性中起作用。在本研究中，我们研究netrin-1在糖尿病小鼠和培养的角膜上皮细胞的角膜上皮伤口愈合，炎症反应和神经纤维再生的调节中的作用。在糖尿病小鼠中，netrin-1的表达与正常小鼠相比降低。此外，高糖阻断了创伤诱导的角膜上皮细胞中netrin-1表达的上调。外源性netrin-1可促进糖尿病小鼠角膜上皮伤口愈合，并通过重新激活高糖处理角膜上皮细胞ERK和EGFR的磷酸化，促进其增殖和迁移。此外，netrin-1减少中性粒细胞浸润，促进M2-巨噬细胞转化，伴随着糖尿病小鼠角膜上皮中促炎因子的表达减弱。netrin-1对角膜上皮创伤愈合和炎症消退的促进作用至少通过腺苷2B受体介导。此外，netrin-1促进了糖尿病小鼠中受损的角膜神经纤维的再生。总之，netrin-1调节糖尿病小鼠角膜上皮创伤愈合、炎症反应和神经纤维再生，表明其在糖尿病角膜病变治疗中的潜在应用。
Netrins are secreted chemoattractants with the roles in axon guidance, cell migration and epithelial plasticity. In the present study, we investigated the roles of netrin-1 in the regulation of corneal epithelial wound healing, inflammation response and nerve fiber regeneration in diabetic mice and cultured corneal epithelial cells. In diabetic mice, the expression of netrin-1 was decreased when compared with that of normal mice. Furthermore, high glucose blocked the wounding-induced up-regulation of netrin-1 expression in corneal epithelial cells. Exogenous netrin-1 promoted the corneal epithelial wound healing in diabetic mice, and facilitated the proliferation and migration by reactivating the phosphorylation of ERK and EGFR in high-glucose treated corneal epithelial cells. Moreover, netrin-1 decreased the neutrophil infiltration and promoted M2 macrophage transition, accompanied with the attenuated expression of pro-inflammatory factors in diabetic mouse corneal epithelium. The promotions of netrin-1 on corneal epithelial wound healing and inflammation resolution were mediated at least through the adenosine 2B receptor. In addition, netrin-1 promoted the regeneration of corneal nerve fibers that was impaired in diabetic mice. Taken together, netrin-1 regulates corneal epithelial wound healing, inflammation response and nerve fiber regeneration in diabetic mice, indicating the potential application for the therapy of diabetic keratopathy.
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影响因子：
4.3
作者：
Misra SL;Patel DV;McGhee CN;Pradhan M;Kilfoyle D;Braatvedt GD;Craig JP
通讯作者：
Craig JP
影响因子：
3.7
作者：
Chen JB;Yang YH;Lee WC;Liou CW;Lin TK;Chung YH;Chuang LY;Yang CH;Chang HW
通讯作者：
Chang HW
DOI：
10.1096/fj.06-7227rev
发表时间：
2007-02
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Serhan CN;Brain SD;Buckley CD;Gilroy DW;Haslett C;O'Neill LA;Perretti M;Rossi AG;Wallace JL
通讯作者：
Wallace JL
DOI：
10.1164/rccm.200905-0717oc
发表时间：
2010-04-15
影响因子：
24.7
作者：
Mirakaj, Valbona;Thix, Cyril A.;Rosenberger, Peter
通讯作者：
Rosenberger, Peter
巨噬细胞耗竭会损害小鼠自体移植后角膜伤口的愈合
影响因子：
3.7
作者：
Li S;Li B;Jiang H;Wang Y;Qu M;Duan H;Zhou Q;Shi W
通讯作者：
Shi W