title: MiR-9 inhibits Schwann cell migration by targeting Cthrc1 following sciatic nerve injury.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Songlin
authors.initials: S
authors.lastname: Zhou
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.forename: Wen
authors.initials: W
authors.lastname: Hu
authors.forename: Tianmei
authors.initials: T
authors.lastname: Qian
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Guohui
authors.initials: G
authors.lastname: Ding
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Gu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002465:Cell Movement; D002478:Cells, Cultured; D015536:Down-Regulation; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D009416:Nerve Regeneration; D059348:Peripheral Nerve Injuries / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C502427:Cthrc1 protein, rat; D006023:Glycoproteins; C582333:MIRN9 microRNA, rat; D035683:MicroRNAs; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein
keywords: CTHRC1; Migration; Peripheral nerve regeneration; Schwann cell; miR-9