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通过表达 MIR155HG 的间充质干细胞改善血管内膜增生的治疗效果，MIR155HG 作为 microRNA-205 的 ceRNA 发挥作用。

Improved therapeutic effects on vascular intimal hyperplasia by mesenchymal stem cells expressing MIR155HG that function as a ceRNA for microRNA-205.

机构信息

Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, China.

Thoracoscopy Institute of Cardiac Surgery, Shandong University, Jinan, China.

出版信息

J Cell Mol Med. 2024 May;28(9):e18351. doi: 10.1111/jcmm.18351.

DOI:10.1111/jcmm.18351
PMID:38693854
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11063722/
Abstract

Coronary artery bypass grafting (CABG) is an effective treatment for coronary heart disease, with vascular transplantation as the key procedure. Intimal hyperplasia (IH) gradually leads to vascular stenosis, seriously affecting the curative effect of CABG. Mesenchymal stem cells (MSCs) were used to alleviate IH, but the effect was not satisfactory. This work aimed to investigate whether lncRNA MIR155HG could improve the efficacy of MSCs in the treatment of IH and to elucidate the role of the competing endogenous RNA (ceRNA). The effect of MIR155HG on MSCs function was investigated, while the proteins involved were assessed. IH was detected by HE and Van Gieson staining. miRNAs as the target of lncRNA were selected by bioinformatics analysis. qRT-PCR and dual-luciferase reporter assay were performed to verify the binding sites of lncRNA-miRNA. The apoptosis, Elisa and tube formation assay revealed the effect of ceRNA on the endothelial protection of MIR155HG-MSCs. We observed that MIR155HG improved the effect of MSCs on IH by promoting viability and migration. MIR155HG worked as a sponge for miR-205. MIR155HG/miR-205 significantly improved the function of MSCs, avoiding apoptosis and inducing angiogenesis. The improved therapeutic effects of MSCs on IH might be due to the ceRNA role of MIR155HG/miR-205.

摘要

冠状动脉旁路移植术（CABG）是治疗冠心病的有效方法，血管移植是关键步骤。内膜增生（IH）逐渐导致血管狭窄，严重影响 CABG 的疗效。间充质干细胞（MSCs）被用于缓解 IH，但效果并不理想。本研究旨在探讨长链非编码 RNA MIR155HG 是否可以提高 MSCs 在 IH 治疗中的疗效，并阐明竞争内源性 RNA（ceRNA）的作用。研究了 MIR155HG 对 MSCs 功能的影响，并评估了涉及的蛋白质。通过 HE 和 Van Gieson 染色检测 IH。通过生物信息学分析选择作为 lncRNA 靶标的 miRNAs。进行 qRT-PCR 和双荧光素酶报告基因检测以验证 lncRNA-miRNA 的结合位点。通过凋亡、Elisa 和管形成试验揭示了 ceRNA 对 MIR155HG-MSCs 内皮保护的影响。我们观察到 MIR155HG 通过促进活力和迁移来改善 MSCs 对 IH 的作用。MIR155HG 作为 miR-205 的海绵。MIR155HG/miR-205 显著改善了 MSCs 的功能，避免了细胞凋亡并诱导了血管生成。MSCs 对 IH 的治疗效果的改善可能归因于 MIR155HG/miR-205 的 ceRNA 作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/552a108bba88/JCMM-28-e18351-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/b8a416fe3b2e/JCMM-28-e18351-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/024070bfd4b3/JCMM-28-e18351-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/6f74d19bfe4c/JCMM-28-e18351-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/546516ea66cd/JCMM-28-e18351-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/96c4b2b92c85/JCMM-28-e18351-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/098bb48c859e/JCMM-28-e18351-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/552a108bba88/JCMM-28-e18351-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/b8a416fe3b2e/JCMM-28-e18351-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/024070bfd4b3/JCMM-28-e18351-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/6f74d19bfe4c/JCMM-28-e18351-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/546516ea66cd/JCMM-28-e18351-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/96c4b2b92c85/JCMM-28-e18351-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/098bb48c859e/JCMM-28-e18351-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d54/11063722/552a108bba88/JCMM-28-e18351-g002.jpg

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Improved therapeutic effects on vascular intimal hyperplasia by mesenchymal stem cells expressing MIR155HG that function as a ceRNA for microRNA-205.

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引用本文的文献

[1]
Therapeutic Potential and Mechanisms of Mesenchymal Stem Cells in Coronary Artery Disease: Narrative Review.

Int J Mol Sci. 2025-6-5

本文引用的文献

[1]
LncRNA MIR155HG Overexpression Promotes Proliferation, Migration, and Chemoresistance in Gastric Cancer Cells.

Int J Med Sci. 2023

[2]
Interplay between LncRNAs and microRNAs in Breast Cancer.

Int J Mol Sci. 2023-4-30

[3]
Graft thrombosis after coronary artery bypass surgery and current practice for prevention.

Front Cardiovasc Med. 2023-3-8

[4]
The effect of lncRNA MIR155HG-modified MSCs and exosome delivery to synergistically attenuate vein graft intimal hyperplasia.

Stem Cell Res Ther. 2022-11-4

[5]
LncRNA Meg3 promotes oxygen and glucose deprivation injury by decreasing angiogenesis in hBMECs by targeting the miR‑122‑5p/NDRG3 axis.

Exp Ther Med. 2022-8-11

[6]
Immunomodulatory Mechanisms of Mesenchymal Stem Cells and Their Potential Clinical Applications.

Int J Mol Sci. 2022-9-2

[7]
Pentoxifylline Prevents Restenosis by Inhibiting Cell Proliferation via p38MAPK Pathway in Rat Vein Graft Model.

Cell Transplant. 2022

[8]
The Etiology and Molecular Mechanism Underlying Smooth Muscle Phenotype Switching in Intimal Hyperplasia of Vein Graft and the Regulatory Role of microRNAs.

Front Cardiovasc Med. 2022-7-28

[9]
Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis.

JAMA. 2022-8-9

[10]
Stem cell-based therapy for human diseases.

Signal Transduct Target Ther. 2022-8-6

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