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Human Cell

pp 1–15 | Cite as

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

  • Chunmei CuiEmail author
  • Yuehua Li
  • Ying Liu
Research Article
  • 16 Downloads

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.

Keywords

MiR-377 Human retinal endothelial cell Angiogenesis Inflammatory response Diabetic retinopathy 

Notes

Author contributions

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.

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors have declared that no competing interests exist.

Supplementary material

13577_2019_240_MOESM1_ESM.doc (4.5 mb)
Supplementary material 1 (DOC 4649 KB)

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Copyright information

© Japan Human Cell Society and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Ophthalmology, Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina

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