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Down-regulation of miR-377 suppresses high glucose and hypoxia-induced angiogenesis and inflammation in human retinal endothelial cells by direct up-regulation of target gene SIRT1

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Abstract

Diabetic retinopathy (DR) is one of the common microvascular complications of diabetes mellitus, which is the main cause of blindness in diabetic patients. Angiogenesis plays an important role in retinal detachment and retinal microvascular inflammation throughout the whole development of DR. This study aimed to investigate the regulatory effect and the potential mechanism of miR-377 on high glucose and hypoxia-induced angiogenesis and inflammation in human retinal endothelial cells, and found that the miR-377 level was significantly increased after high glucose and hypoxia-mimetic agent to simulate the DR milieu. Moreover, miR-377 was confirmed to directly decrease target SIRT1 gene, further aggravated proliferation, cell cycle transition, migration and angiogenesis, pro-inflammatory molecules release induced by high glucose and hypoxia in vitro. Conversely, down-regulation of miR-377 enhanced expression of SIRT1 and in turn alleviated high glucose and hypoxia-induced angiogenesis and inflammation in vitro. Additionally, Western blot results showed that down-regulation of miR-377 restrained high glucose and hypoxia-induced protein expressions of p-IκBα, nuclear P65 and p-P65. Conversely, up-regulation of miR-377 presented opposite results. Conclusively, down-regulation of miR-377 could partially suppress high glucose and hypoxia-induced angiogenic functions, restrain pro-inflammatory cytokines release, and its mechanism may though inhibition of NF-κB pathway by direct up-regulation of target gene SIRT1 expression. Our study suggests that miR-377 may be used as a potential novel target for prevention strategy for DR.

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Data Availability

All data are included in this published article. Any additional information related to this study is available from the author for correspondence upon reasonable request.

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Authors and Affiliations

  1. Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongti South Road, Chaoyang District, Beijing, 100020, China

    Chunmei Cui, Yuehua Li & Ying Liu

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  1. Chunmei Cui
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  2. Yuehua Li
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  3. Ying Liu
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CC and YL carried out the study and the data statistics. CC participated in study design and drafted the manuscript. YL participated in study design and scientific discussion of the data.

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Correspondence to Chunmei Cui.

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Cui, C., Li, Y. & Liu, Y. Down-regulation of miR-377 suppresses high glucose and hypoxia-induced angiogenesis and inflammation in human retinal endothelial cells by direct up-regulation of target gene SIRT1. Human Cell 32, 260–274 (2019). https://doi.org/10.1007/s13577-019-00240-w

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