Effect of MicroRNA-126a-3p on Bone Marrow Mesenchymal Stem Cells Repairing Blood-brain Barrier and Nerve Injury after Intracerebral Hemorrhage

MicroRNA-126a-3p对骨髓间充质干细胞修复脑出血后血脑屏障及神经损伤的影响

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作者:Chunyan Wang, Jingwei Cao, Shurong Duan, Ran Xu, Hongli Yu, Xin Huo, Yuanyuan Qian

Conclusions

All data illustrate that miR-126-modified MSCs repair BBB and nerve injury after ICH.

Methods

In this study, we isolated, cultured and identified bone marrow mesenchymal stem cells (MSCs) in vitro. Further, the MSCs (transfected with lentivirus expressing microRNA-126a-3p (miR-126)) were injected into the type Ⅶ collagenase-induced ICH rats to investigate the recovery effects of blood-brain barrier (BBB) and nerve damage in vivo.

Objective

Intracerebral hemorrhage (ICH) is a disease that threatens human health due to its high morbidity and mortality. On behalf of finding the better

Results

The MSCs surface marker molecules (CD29: 98.5%; CD90: 96.5%) were highly expressed, and the blood cell surface molecule was negatively expressed (CD45: 2%). Meanwhile, it was verified that miR-126 facilitated the differentiation of MSCs into vascular endothelial cells, owing to the rise of markers (CD31 and VE-cadherin). The modified neurological severity score, modified limb placing test score, brain water content and evans blue content were reduced after transplanted miR-126-modified MSCs. It was found that miR-126 accelerated the differentiation of MSCs into vascular endothelial cells via immunohistochemical staining in vivo. HE staining indicated the area of edema was obviously decreased compared with that in ICH + vector-MSCs group. MiR-126-modified MSCs alleviated the cell apoptosis in brain tissues by TUNEL assay. In addition, the mRNA and protein expression of protease activated receptor-1 and matrix metalloproteinase-9 were diminished, whilst the expression of zonula occludens-1 (ZO-1) and claudin-5 were enhanced in ICH+miR-126-MSCs group. Immunofluorescence assay revealed that miR-126-modified MSCs decreased the disruption of tight junction (ZO-1 and claudin-5). Conclusions: All data illustrate that miR-126-modified MSCs repair BBB and nerve injury after ICH.

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