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Role of Exosomes Derived from miR-133b Modified MSCs in an Experimental Rat Model of Intracerebral Hemorrhage

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Abstract

Intracerebral hemorrhage (ICH) has poor outcomes due to high mortality and morbidity, but until now, the effective treatments remain limited. MicroRNAs (miRNAs) are vital regulators of gene expression and demonstrated to be linked to the pathogenesis of various central nervous system (CNS) diseases. Exosomes are considered as cell-to-cell communication vectors and secreted largely by mesenchymal stromal cells (MSCs). The present study investigated the role of miR-133b delivered by exosomes secreted from MSCs to brain tissues in rats after ICH. An autologous arterial blood ICH model in adult male Sprague–Dawley (SD) rats was used in this study. At 72 h after transfection with miR-133b mimics in MSCs, miR-133b-modified MSC-derived exosomes were collected from medium of MSCs and then injected to rats via tail vein. The levels of miR-133b in secreted exosomes and brain tissues of rats in various groups and the levels of RhoA, phosphorylations of extracellular signal regulating kinase (ERK1/2), and cAMP response element-binding protein (CREB) were detected by real-time PCR and western blot analysis, respectively. The effects of miR-133b on neuronal apoptosis and degeneration were respectively evaluated by TUNEL and fluoro-jade B staining. The miR-133b levels were reduced in brain tissues of rats at 24 h and peaked at 72 h after ICH. At 24 h after miR-133b-modified exosome administration, the level of miR-133b was significantly increased, while the apoptotic and neurodegenerative neurons were obviously reduced in brain tissues after ICH. The results of western blot analysis showed that miR-133b modified exosomes treatment remarkably suppressed RhoA expression and activated ERK1/2/CREB in brain tissues after ICH. Collectively, our investigation suggested that exosomes derived from miR-133b modified MSCs exhibited neuroprotective role for anti-apoptotic effect of miR-133b mediating RhoA and ERK1/2/CREB in rats after ICH.

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Abbreviations

ICH:

Intracerebral hemorrhage

CNS:

Central nervous system

MSCs:

Mesenchymal stromal cells

ERK1/2:

Extracellular signal regulating kinase

CREB:

cAMP response element-binding protein

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling

FJB:

Fluoro-jade B

SBI:

Secondary brain injury

ROS:

Reactive oxygen species

SCI:

Spinal cord injury

ADSCs:

Adipose-derived stem cells

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Funding

This work was supported by National Natural Science Foundation of China (No. 81501005), grants from the China Postdoctoral Science Foundation (Nos. 2016M591912, 2015M580465), and grants from Jiangsu Planned Projects for Postdoctoral Research Funds (No.1501064A).

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Author notes

  1. Haitao Shen and Xiyang Yao are contributed equally to this work, co-first authors.

Authors and Affiliations

  1. Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu Province, 215006, China

    Haitao Shen, Xiyang Yao, Haiying Li, Xiang Li, Tiejun Zhang, Qing Sun, Chengyuan Ji & Gang Chen

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  1. Haitao Shen
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  2. Xiyang Yao
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  3. Haiying Li
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  4. Xiang Li
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  6. Qing Sun
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  7. Chengyuan Ji
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  8. Gang Chen
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Corresponding authors

Correspondence to Qing Sun or Chengyuan Ji.

Ethics declarations

All animal experiments were approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and were performed in accordance with the guidelines of the National Institutes of Health on the care and use of animals.

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Shen, H., Yao, X., Li, H. et al. Role of Exosomes Derived from miR-133b Modified MSCs in an Experimental Rat Model of Intracerebral Hemorrhage. J Mol Neurosci 64, 421–430 (2018). https://doi.org/10.1007/s12031-018-1041-2

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  • DOI: https://doi.org/10.1007/s12031-018-1041-2

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