期刊
JOURNAL OF CELL SCIENCE
卷 127, 期 5, 页码 967-976出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.131672
关键词
miR-9; Schwann cell; Migration; CTHRC1; Peripheral nerve regeneration
类别
资金
- National Key Basic Research Program of China [2014CB542202]
- 863 Program [2012AA020502]
- National Natural Science Foundation of China [81130080, 81171180, 81371389, 31100761, 31371062]
- New Century Excellent Talents in University [NCET-12-0742]
The regulative effects of microRNAs (miRNAs) on responses of Schwann cells to a nerve injury stimulus are not yet clear. In this study, we noted that the expression of eight miRNAs was downregulated at different time points following rat sciatic nerve transection, and found that 368 potential targets of these eight miRNAs were mainly involved in phenotypic modulation of Schwann cells. Of these miRNAs, miR-9 was identified as an important functional regulator of Schwann cell migration that was a crucial regenerative response of Schwann cells to nerve injury. In vitro, upregulated expression of miR-9 inhibited Schwann cell migration, whereas silencing of miR-9 promoted Schwann cell migration. Intriguingly, miR-9 exerted this regulative function by directly targeting collagen triple helix repeat containing protein 1 (CTHRC1), which in turn inactivated downstream Rac1 GTPase. Rac1 inhibitor reduced the promotive effects of anti-miR-9 on Schwann cell migration. In vivo, high expression of miR-9 reduced Schwann cell migration within a regenerative nerve microenvironment. Collectively, our results confirmed the role of miR-9 in regulating Schwann cell migration after nerve injury, thus offering a new approach to peripheral nerve repair.
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