Research Paper Volume 10, Issue 6 pp 1474—1488

microRNA-21 regulates astrocytic reaction post-acute phase of spinal cord injury through modulating TGF-β signaling

Ronghan Liu 1, , Wenzhao Wang 1, , Shuya Wang 1, , Wei Xie 2, , Hongfei Li 1, , Bin Ning 1, ,

  • 1 Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China
  • 2 Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, China

received: May 3, 2018 ; accepted: June 14, 2018 ; published: June 23, 2018 ;

https://doi.org/10.18632/aging.101484
How to Cite

Copyright: Liu et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Astrogliosis following spinal cord injury (SCI) was considered as a negative factor for neural regeneration. We found that miR-21 was significantly upregulated after SCI. So, we aim to determine whether miR-21 acts in a positive manner post SCI. In vitro, we measured the proliferation, apoptosis and cytokine secretion of primary cultured astrocytes after modulating the expression of miR-21 by western blot, RT-PCR and immunofluorescence. In vivo, we performed a modified Allen’s weight drop model. Manipulation of the miR-21 expression level was achieved by interfering with antagomir and agomir. Clinic score was evaluated and recorded every day. Then, western blot, immunohistochemistry, TUNEL assay and ELISA were performed to detect pathological and functional alterations. Our results demonstrate that miR-21 can modulate the secretion, proliferation and apoptosis of astrocytes to promote recovery after SCI both in vivo and in vitro. These effects are likely mediated through transforming growth factor beta mediated targeting of the PI3K/Akt/mTOR pathway. These data suggest that miR-21 can regulate astrocytic function, then promote the functional recovery after SCI. We therefore highlight the positive effects of miR-21 after SCI.

Abbreviations

SCI: spinal cord injury; CSPGs: chondroitin sulfate proteoglycans; GFAP: glial fibrillary acidic protein; BDNF: brain-derived neurotrophic factor; TGF-β1: transforming growth factor-beta1; PTEN: phosphatase and tensin homologue deleted on chromosome 10; PI3K/Akt/mTOR: phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin; NGF: nerve growth factor; miRs: microRNAs.