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Exosomal microRNA-133b-3p from bone marrow mesenchymal stem cells inhibits angiogenesis and oxidative stress via FBN1 repression in diabetic retinopathy

Gene Therapy volume 29, pages 710–719 (2022)Cite this article

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Abstract

Diabetic retinopathy (DR) is a common microvascular complication. Many studies have focused on the role of microRNAs (miRNAs) in DR but not specifically on miR-133b-3p. Thus, this study is to unmask the mechanisms of miR-133b-3p in DR. KK/Upj-Ay mice (a spontaneous diabetic nephropathy model of DM, referred to as DR mice) were used in the study, and retinal tissues were collected. Bone marrow mesenchymal stem cells (BMSCs) were isolated and identified. High glucose (HG)-treated mouse retinal microvascular endothelial cells (mRMECs) were transfected or co-cultured with BMSCs-derived exosomes. Then, cell proliferation, migration, apoptosis, angiogenesis, and oxidative stress were observed. MiR-133b-3p and FBN1 expression in tissues and cells was detected. MiR-133b-3p expression was reduced, and FBN1 expression was increased in retinal tissues of DR mice and HG-treated mRMECs. Up-regulating miR-133b-3p or down-regulating FBN1 or BMSCs-derived exosomes impaired oxidative stress, angiogenesis, proliferation, migration, and promoted apoptosis of HG-treated mRMECs. This study has elucidated that exosomal miR-133b-3p from BMSCs suppresses angiogenesis and oxidative stress in DR via FBN1 repression.

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Fig. 1: miR-133b-3p is down-regulated and FBN1 is up-regulated in retinal tissues of mice with DR.
Fig. 2: miR-133b-3p and FBN1 levels in mRMECs after transfection.
Fig. 3: Isolation and identification of mouse BMSCs and BMSCs-derived exosomes.
Fig. 4: Uptake of exosomes by mRMECs; changes of miR-133b-3p and FBN1 expression in exosomes and mRMECs.
Fig. 5: Up-regulation of miR-133b-3p or down-regulation of FBN1 or BMSCs-derived exosomes relieves oxidative stress HG-treated mRMECs.
Fig. 6: Up-regulation of miR-133b-3p or down-regulation of FBN1 or BMSCs-derived exosomes inhibit angiogenesis of HG-treated mRMECs.
Fig. 7: Up-regulation of miR-133b-3p or down-regulation of FBN1 or BMSCs-derived exosomes inhibit proliferation, migration and promote apoptosis of HG-treated mRMECs.
Fig. 8: MiR-133b-3p targets FBN1.

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Acknowledgements

We would like to acknowledge the reviewers for their helpful comments on this paper.

Funding

This work was supported by the Natural Science Foundation of Guangxi (Grant/Award number:2020GXNSFAA259054) and First Batch of High-level Talent Scientific Research Projects of the Affiliated Hospital of Youjiang Medical University for Nationalities in 2019 (Grant/Award number:R20196340 & Y20196304)).

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Authors and Affiliations

  1. Department of Ophthalmology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China

    Gaohua Liang, Zhiliang Qin, Yanni Luo, Zhimin Shi, Rizhang Wei & Wenhao Ma

  2. Department of Ophthalmology, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, Guangdong, China

    Jiayang Yin

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Contributions

WM contributed to study design; GL contributed to manuscript editing; ZQ, YL, and JY contributed to experimental studies; ZS and RW contributed to data analysis.

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Correspondence to Wenhao Ma.

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Liang, G., Qin, Z., Luo, Y. et al. Exosomal microRNA-133b-3p from bone marrow mesenchymal stem cells inhibits angiogenesis and oxidative stress via FBN1 repression in diabetic retinopathy. Gene Ther 29, 710–719 (2022). https://doi.org/10.1038/s41434-021-00310-5

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