MicroRNA-150 and its target ETS-domain transcription factor 1 contribute to inflammation in diabetic photoreceptors.
MicroRNA-150 and its target ETS-domain transcription factor 1 contribute to inflammation in diabetic photoreceptors.
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DOI：
10.1111/jcmm.17012
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发表时间：
2021-11
影响因子：
5.3
通讯作者：
Ko GY
中科院分区：
文献类型：
--
作者：
Yu F;Ko ML;Ko GY
由于肥胖流行，肥胖相关的2型糖尿病（T2 D）在美国呈上升趋势，60%的T2 D患者在其一生中发展为糖尿病视网膜病变（DR）。慢性炎症是肥胖和T2 D的标志，也是公认的DR的主要原因，视网膜光感受器是眼内炎症的主要来源，直接导致糖尿病血管异常。然而，糖尿病损伤如何引起感光细胞炎症还不清楚。在这项研究中，我们使用高脂饮食（HFD）诱导的T2 D小鼠模型和培养的棕榈酸（PA）处理的光感受器来破译介导高脂诱导的光感受器炎症的主要参与者。我们发现，在PA引起的光感受器炎症中，PA引起的microRNA-150（miR-150）随着ETS结构域转录因子1（Elk 1）（miR-150的下游靶点）的一致上调而减少。我们比较了喂食HFD的野生型（WT）和miR-150 null（miR-150−/−）小鼠，发现miR-150的缺失与ELK 1的上调一起加剧了HFD诱导的感光细胞炎症。我们进一步描绘了丝氨酸383（pELK 1 S383）磷酸化ELK 1的关键细胞定位，并发现miR-150减少通过上调ELK 1和pELK 1 S383加剧了光感受器中T2 D诱导的炎症，ELK 1的敲低减轻了PA诱导的光感受器炎症。
Obesity‐associated type 2 diabetes (T2D) is on the rise in the United States due to the obesity epidemic, and 60% of T2D patients develop diabetic retinopathy (DR) in their lifetime. Chronic inflammation is a hallmark of obesity and T2D and a well‐accepted major contributor to DR, and retinal photoreceptors are a major source of intraocular inflammation and directly contribute to vascular abnormalities in diabetes. However, how diabetic insults cause photoreceptor inflammation is not well known. In this study, we used a high‐fat diet (HFD)‐induced T2D mouse model and cultured photoreceptors treated with palmitic acid (PA) to decipher major players that mediate high‐fat‐induced photoreceptor inflammation. We found that PA‐elicited microRNA‐150 (miR‐150) decreases with a consistent upregulation of ETS‐domain transcription factor 1 (Elk1), a downstream target of miR‐150, in PA‐elicited photoreceptor inflammation. We compared wild‐type (WT) and miR‐150 null (miR‐150−/−) mice fed with an HFD and found that deletion of miR‐150 exacerbated HFD‐induced photoreceptor inflammation in conjunction with upregulated ELK1. We further delineated the critical cellular localization of phosphorylated ELK1 at serine 383 (pELK1S383) and found that decreased miR‐150 exacerbated the T2D‐induced inflammation in photoreceptors by upregulating ELK1 and pELK1S383, and knockdown of ELK1 alleviated PA‐elicited photoreceptor inflammation.
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影响因子：
1.8
作者：
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通讯作者：
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影响因子：
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作者：
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Ko GY
DOI：
10.1073/pnas.1314575110
发表时间：
2013-10-08
影响因子：
11.1
作者：
Du, Yunpeng;Veenstra, Alexander;Kern, Timothy S.
通讯作者：
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