Decreased MicroRNA-150 Exacerbates Neuronal Apoptosis in the Diabetic Retina.
Decreased MicroRNA-150 Exacerbates Neuronal Apoptosis in the Diabetic Retina.
复制标题
微小RNA - 150表达降低加剧糖尿病视网膜病变中的神经元凋亡。
DOI：
10.3390/biomedicines9091135
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发表时间：
2021-09-01
期刊：
影响因子：
4.7
通讯作者：
Ko GY
中科院分区：
文献类型：
--
作者：
Yu F;Ko ML;Ko GY
糖尿病视网膜病变(DR)是一种与糖尿病相关的慢性并发症，也是美国职场成年人失明的头号原因。超过90%的糖尿病患者有肥胖相关的2型糖尿病(T2D)，60%的T2D患者会发生DR，糖尿病发作后不久光感受器就会发生细胞凋亡，从而导致视网膜功能障碍和导致视力障碍的微血管并发症。然而，糖尿病患者的侮辱是如何导致光感受器凋亡的，目前还不清楚。在这项研究中，肥胖相关的T2D小鼠和培养的光感受器被用来研究microRNA-150(miR-150)及其下游靶基因如何参与光感受器的凋亡。在T2D视网膜中，miR-150随着其靶Ets区转录因子(ELK1)和苏氨酸417位的磷酸化ELK1(PELK1T417)上调而降低。在培养的光感受器中，用棕榈酸(PA)模拟高脂肪环境，降低miR-150，但上调ELK1，pELK1T417，以及pELK1T417从细胞质到细胞核的移位。MiR-150(miR-150−/−)缺失可加剧T2D或PA诱导的光感受器细胞凋亡。用针对ELK1的小干扰RNA(SiRNA)阻断ELK1的表达并不能挽救PA诱导的光感受器凋亡。PELK1T417从胞浆到胞核的移位似乎是糖尿病诱导的光感受器细胞凋亡的关键步骤。
Diabetic retinopathy (DR) is a chronic complication associated with diabetes and the number one cause of blindness in working adults in the US. More than 90% of diabetic patients have obesity-associated type 2 diabetes (T2D), and 60% of T2D patients will develop DR. Photoreceptors undergo apoptosis shortly after the onset of diabetes, which contributes to the retinal dysfunction and microvascular complications leading to vision impairment. However, how diabetic insults cause photoreceptor apoptosis remains unclear. In this study, obesity-associated T2D mice and cultured photoreceptors were used to investigate how decreased microRNA-150 (miR-150) and its downstream target were involved in photoreceptor apoptosis. In the T2D retina, miR-150 was decreased with its target ETS-domain transcription factor (ELK1) and phosphorylated ELK1 at threonine 417 (pELK1T417) upregulated. In cultured photoreceptors, treatments with palmitic acid (PA), to mimic a high-fat environment, decreased miR-150 but upregulated ELK1, pELK1T417, and the translocation of pELK1T417 from the cytoplasm to the cell nucleus. Deletion of miR-150 (miR-150−/−) exacerbates T2D- or PA-induced photoreceptor apoptosis. Blocking the expression of ELK1 with small interfering RNA (siRNA) for Elk1 did not rescue PA-induced photoreceptor apoptosis. Translocation of pELK1T417 from cytoplasm-to-nucleus appears to be the key step of diabetic insult-elicited photoreceptor apoptosis.
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