A regulatory role for β-adrenergic receptors regarding the resolvin D1 (RvD1) pathway in the diabetic retina.
A regulatory role for β-adrenergic receptors regarding the resolvin D1 (RvD1) pathway in the diabetic retina.
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DOI：
10.1371/journal.pone.0185383
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Berger EA
中科院分区：
文献类型：
--
作者：
Shi H;Carion TW;Jiang Y;Chahine A;Steinle JJ;Berger EA
糖尿病视网膜病变是一种视力衰弱的疾病，治疗选择有限。化合物49 b是一种β-肾上腺素能受体激动剂，已被证明可有效降低与糖尿病视网膜病变相关的疾病发病机制。虽然确切的机制还不完全清楚，但以前的研究已经确定它可以减少促炎细胞因子TNF-α，并抑制视网膜微血管培养物的凋亡。随着炎症在驱动疾病发病机制中变得越来越被认可，作为干预治疗点的促消退途径的调节也是如此。目前的研究试图探索化合物49 b是否对促消退途径有任何影响，从而有助于改善疾病结果。使用体内（1型糖尿病动物模型）和体外（视网膜内皮细胞、Müller细胞、中性粒细胞/PMN）技术，确定高葡萄糖降低促消退脂质介质消退素D1（RvD 1）水平，并差异性改变所需的酶5-脂氧合酶（5-LOX）、15-LOX-1和15-LOX-2。RvD 1受体甲酰肽受体2（ALX/FPR 2）和G蛋白偶联受体32（GPR 32）也在高血糖条件下下调。此外，观察到β-肾上腺素能受体激活恢复了体内和体外观察到的高葡萄糖诱导的酶活性和RvD 1水平降低。目前的研究是第一个描述β-肾上腺素能受体对促消退途径的调节作用。
Diabetic retinopathy is a visually debilitating disease with limited treatment options available. Compound 49b, a β-adrenergic receptor agonist, has been demonstrated to effectively reduce disease pathogenesis associated with diabetic retinopathy. While the exact mechanisms are not fully understood, previous studies have determined that it reduces the pro-inflammatory cytokine, TNF-α, and inhibits apoptosis of the retinal microvasculture. As inflammation becomes more recognized in driving disease pathogenesis, so does the regulation by pro-resolving pathways as therapeutic points of intervention. The current study sought to explore whether Compound 49b had any influence on pro-resolving pathways, thus contributing to improved disease outcome. Using in vivo (animal model of type 1 diabetes) and in vitro (retinal endothelial cells, Müller cells, neutrophils/PMN) techniques, it was determined that high glucose lowers pro-resolving lipid mediator, resolvin D1 (RvD1) levels and differentially alters required enzymes, 5-lipoxygenase (5-LOX), 15-LOX-1 and 15-LOX-2. RvD1 receptors formyl peptide receptor 2 (ALX/FPR2) and G-protein coupled receptor 32 (GPR32) were also downregulated in response to hyperglycemic conditions. Moreover, it was observed that β-adrenergic receptor activation restored high glucose-induced decreases in both enzyme activity and RvD1 levels observed in vivo and in vitro. The current study is the first to describe a regulatory role for β-adrenergic receptors on pro-resolving pathways.
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影响因子：
--
作者：
Kern, Timothy S.
通讯作者：
Kern, Timothy S.
IL-13通过15-脂氧合酶/G蛋白受体激酶2机制在人气道上皮细胞中脱敏的β2-肾上腺素受体。
DOI：
10.1016/j.jaci.2015.02.006
发表时间：
2015-05
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Albano GD;Zhao J;Etling EB;Park SY;Hu H;Trudeau JB;Profita M;Wenzel SE
通讯作者：
Wenzel SE
DOI：
10.1161/atvbaha.112.249508
发表时间：
2012-08
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Norling LV;Dalli J;Flower RJ;Serhan CN;Perretti M
通讯作者：
Perretti M
影响因子：
4.4
作者：
Chen, WQ;Esselman, WJ;Busik, JV
通讯作者：
Busik, JV
影响因子：
3.3
作者：
Wang, Jun;Li, Jing;Wu, Gen-Cheng
通讯作者：
Wu, Gen-Cheng