Liraglutide attenuates the migration of retinal pericytes induced by advanced glycation end products
Liraglutide attenuates the migration of retinal pericytes induced by advanced glycation end products
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利拉鲁肽减弱晚期糖基化终产物诱导的视网膜周细胞的迁移
DOI：
10.1016/j.peptides.2018.05.003
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发表时间：
2018-07-01
期刊：
影响因子：
3
通讯作者：
Kuang, Hong-yu
中科院分区：
文献类型：
--
作者：
Lin, Wen-jian;Ma, Xue-fei;Kuang, Hong-yu
视网膜周细胞迁移是糖尿病视网膜病变(DR)中周细胞丢失的一种新机制，在血-视网膜屏障(BRB)早期损害中起重要作用。胰升糖素样肽-1(GLP-1)在糖尿病视网膜病变早期具有保护作用，但GLP-1与视网膜周细胞的关系尚不清楚。在这项研究中，晚期糖基化终产物(AGEs)显著增加了原代牛视网膜周细胞的迁移，而不影响细胞的活力。AGEs还显著增强磷脂酰肌醇3-激酶(PI3K)/Akt的激活，并改变迁移相关蛋白的表达，包括磷酸化粘着斑激酶(p-FAK)、基质金属蛋白酶(MMP)-2和纽蛋白。抑制PI3K可显著减弱AGEs诱导的视网膜周细胞迁移，逆转基质金属蛋白酶-2的过度表达。视网膜周细胞表达胰高血糖素样肽-1受体(GLP1R)，GLP-1类似物利拉鲁肽显著抑制GLP1R诱导的周细胞迁移，并逆转AGEs诱导的p-Akt/Akt、p-FAK/FAK、vinculin和MMP2水平的变化，提示利拉鲁肽的保护作用与PI3K/Akt信号通路有关。这些结果为视网膜周细胞迁移的机制提供了新的见解。早期应用利拉鲁肽对周细胞迁移具有潜在的调控作用，这可能有助于维持血管屏障的完整性，延缓DR的发生发展。
Retinal pericyte migration represents a novel mechanism of pericyte loss in diabetic retinopathy (DR), which plays a crucial role in the early impairment of the blood-retinal barrier (BRB). Glucagon-like peptide-1 (GLP-1) has been shown to protect the diabetic retina in the early stage of DR; however, the relationship between GLP-1 and retinal pericytes has not been discussed. In this study, advanced glycation end products (AGEs) significantly increased the migration of primary bovine retinal pericytes without influencing cell viability. AGEs also significantly enhanced phosphatidylinositol 3-kinase (PI3K)/Akt activation, and changed the expressions of migration-related proteins, including phosphorylated focal adhesion kinase (p-FAK), matrix metalloproteinase (MMP)-2 and vinculin. PI3K inhibition significantly attenuated the AGEs-induced migration of retinal pericytes and reversed the overexpression of MMP-2. Glucagon-like peptide-1 receptor (Glp1r) was expressed in retinal pericytes, and liraglutide, a GLP-1 analog, significantly attenuated the migration of pericytes by Glp1r and reversed the changes in p-Akt/Akt, p-FAK/FAK, vinculin and MMP-2 levels induced by AGEs, indicating that the protective effect of liraglutide was associated with the PI3K/Akt pathway. These results provided new insights into the mechanism underlying retinal pericyte migration. The early use of liraglutide exerts a potential bebefical effect on regulating pericyte migration, which might contribute to mechanisms that maintain the integrity of vascular barrier and delay the development of DR.