Vascular Microenvironment Laboratory, Department of Pharmacology, College of Medicine, Seoul National University, Seoul, South Korea.
Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
FASEB J. 2018 May;32(5):2324-2338. doi: 10.1096/fj.201700570RR. Epub 2017 Dec 21.
Pericytes (PCs) are crucial in maintaining the quiescence of endothelial cells (ECs) and the integrity of EC tight junctions. Especially in diabetic retinopathy (DR), PC loss is one of the early pathologic changes in capillaries of diabetic retinas. Thus, preventing PC loss is beneficial for attenuating vision impairment in patients with DR. Although many studies have revealed the mechanism of PC loss in retinas, little is known about the mechanisms that increase PC survival. We focused on the effect of β-adrenergic receptor agonists (β-agonists) on PC loss in diabetic retinas. In this study, β-agonists increased the cell viability of PCs by increasing PC survival and proliferation. Mechanistically, β-agonist-induced protein kinase B activation in PCs reduced PC apoptosis in response to various stimuli. β2-agonists more potently increased PC survival than β1-agonists. β2-Agonist reduced vascular leakage and PC loss in retinas of mice with streptozotocin-induced diabetes. In cocultures of PCs and ECs, β2-agonists restored the altered permeability and ZO-1 expression in ECs induced by PC loss. We concluded that β-agonists, especially β2-agonists, increase PC survival, thereby preventing diabetes-induced PC loss in retinas. These results provide a potential therapeutic benefit of β-agonists for preventing PC loss in DR.-Yun, J.-H., Jeong, H.-S., Kim, K.-J., Han, M. H., Lee, E. H., Lee, K., Cho, C.-H. β-Adrenergic receptor agonists attenuate pericyte loss in diabetic retinas through Akt activation.
周细胞（PCs）在维持内皮细胞（ECs）的静止状态和 EC 紧密连接的完整性方面起着至关重要的作用。特别是在糖尿病视网膜病变（DR）中，PC 丢失是糖尿病视网膜毛细血管早期病变之一。因此，防止 PC 丢失有利于减轻 DR 患者的视力损害。尽管许多研究已经揭示了视网膜中 PC 丢失的机制，但对于增加 PC 存活的机制知之甚少。我们专注于β-肾上腺素能受体激动剂（β-agonists）对糖尿病视网膜中 PC 丢失的影响。在这项研究中，β-激动剂通过增加 PC 的存活和增殖来提高 PC 的细胞活力。从机制上讲，PC 中的β-激动剂诱导的蛋白激酶 B 激活可减少对各种刺激的 PC 凋亡。β2-激动剂比β1-激动剂更有效地增加 PC 的存活。β2-激动剂可减少链脲佐菌素诱导的糖尿病小鼠视网膜中的血管渗漏和 PC 丢失。在 PC 和 EC 的共培养物中，β2-激动剂可恢复由 PC 丢失引起的 EC 通透性和 ZO-1 表达的改变。我们得出结论，β-激动剂，特别是β2-激动剂，可增加 PC 的存活，从而防止糖尿病引起的视网膜 PC 丢失。这些结果为β-激动剂预防 DR 中 PC 丢失提供了潜在的治疗益处。
