Müller glia-derived exosomal miR-9-3p promotes angiogenesis by restricting sphingosine-1-phosphate receptor S1P(1) in diabetic retinopathy.
Müller glia-derived exosomal miR-9-3p promotes angiogenesis by restricting sphingosine-1-phosphate receptor S1P(1) in diabetic retinopathy.
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Müller 胶质细胞来源的外泌体 miR-9-3p 通过限制糖尿病视网膜病变中的 1-磷酸鞘氨醇受体 S1P1 促进血管生成
DOI：
10.1016/j.omtn.2021.12.019
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发表时间：
2022-03-08
期刊：
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Liu Y;Yang Q;Fu H;Wang J;Yuan S;Li X;Xie P;Hu Z;Liu Q
糖尿病视网膜病变是一种异质性视网膜变性疾病，微血管功能障碍被认为是晚期的标志。在这项研究中，我们证明了从增殖性糖尿病视网膜病变患者的玻璃体液中收集的外泌体通过其升高的miR-9- 3 p表达水平促进原代人视网膜内皮细胞的增殖、迁移和管形成能力。Müller胶质细胞被进一步认为是异常表达的miR-9- 3 p的唯一来源，体外和体内实验都证实了Müller胶质细胞衍生的外泌体在高糖下加重血管功能障碍。从机制上讲，外泌体miRNA-9- 3 p转移到视网膜内皮细胞并与鞘氨醇-1-磷酸受体S1 P1编码序列结合，随后在存在或不存在外源性VEGF-A的情况下激活VEGFR 2磷酸化和内化。我们成功地协调了视网膜Müller胶质细胞和内皮细胞在病理状态下的动态串扰，这可能为糖尿病视网膜病变的治疗提供新的生物标志物或有前途的治疗药物。Liu等人显示，在糖尿病视网膜病变患者的玻璃体液中，由Müller细胞分泌的外泌体miRNA-9- 3 p通过限制鞘氨醇-1-磷酸受体S1 P1促进视网膜血管生成。这提供了对糖尿病视网膜病变潜在分子机制的更好理解，并为未来新的潜在治疗靶点提供了线索。
Diabetic retinopathy is a heterogeneous retinal degenerative disease with the microvascular dysfunction being recognized as a hallmark of the advanced stage. In this study, we demonstrated that exosomes collected from the vitreous humor of proliferative diabetic retinopathy patients promoted proliferation, migration and tube formation ability of primary human retinal endothelial cells via its elevated miR-9-3p expression level. Müller glia cells were further recognized as the sole source of the aberrantly expressed miR-9-3p, and both in vitro and in vivo experiments validated that Müller glia-derived exosomes aggravate vascular dysfunction under high glucose. Mechanistically, exosomal miRNA-9-3p was transferred to retinal endothelial cells and bound to the sphingosine-1-phosphate receptor S1P1 coding sequence, which subsequently activated VEGFR2 phosphorylation and internalization in the presence or absence of exogenous VEGF-A. We successfully orchestrated the dynamic crosstalk between retinal Müller glia cells and endothelial cells in pathological condition, which may provide a novel biomarker or promising therapeutic agents for the treatment of diabetic retinopathy. Liu et al. show that, in the vitreous humor of diabetic retinopathy patients, exosomal miRNA-9-3p secreted by Müller cells promote retinal angiogenesis by restricting sphingosine-1-phosphate receptor S1P1. This provides a better understanding on molecular mechanisms underlying diabetic retinopathy and sheds light on new potential therapeutic targets in future.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
DOI：
10.1007/978-3-030-27378-1_4
发表时间：
2019-01-01
期刊：
RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY
影响因子：
--
作者：
Klingeborn, Mikael;Skiba, Nikolai P.;Rickman, Catherine Bowes
通讯作者：
Rickman, Catherine Bowes
影响因子：
9.3
作者：
Kokona, Despina;Ebneter, Andreas;Zinkernagel, Martin S.
通讯作者：
Zinkernagel, Martin S.
影响因子：
14.8
作者：
Kee, Nohjin;Teixeira, Catia M.;Frankland, Paul W.
通讯作者：
Frankland, Paul W.
MiR-9 促进肿瘤发生和血管生成，并在人胶质瘤中被 MYC 和 OCT4 激活
DOI：
10.1186/s13046-019-1078-2
发表时间：
2019-02-22
影响因子：
11.3
作者：
Chen, Xu;Yang, Fan;Wang, Tao
通讯作者：
Wang, Tao