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Inhibition of KLF7-Targeting MicroRNA 146b Promotes Sciatic Nerve Regeneration

Overview
Journal Neurosci Bull
Specialty Neurology
Date 2018 Jan 23
PMID 29356943
Citations 15
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Abstract

A previous study has indicated that Krüppel-like factor 7 (KLF7), a transcription factor that stimulates Schwann cell (SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of microRNA-146b (miR-146b) affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with miRNA lentivirus, miRNA inhibitor lentivirus, or KLF7 siRNA lentivirus in vitro. The expression of miR146b and KLF7, as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft (ANA) followed by injection of GFP control vector or a lentiviral vector encoding an miR-146b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. miR-146b directly targeted KLF7 by binding to the 3'-UTR, suppressing KLF7. Up-regulation of miR-146b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing miR-146b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which miR-146b was expressed in vivo. Similarly, 4 weeks after the ANA, anti-miR-146b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0 (anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by miR-146b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.

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References
1.
Bremer J, OConnor T, Tiberi C, Rehrauer H, Weis J, Aguzzi A . Ablation of Dicer from murine Schwann cells increases their proliferation while blocking myelination. PLoS One. 2010; 5(8):e12450. PMC: 2929198. DOI: 10.1371/journal.pone.0012450. View

2.
Byers J, Huguenard A, Kuruppu D, Liu N, Xu X, Sengelaub D . Neuroprotective effects of testosterone on motoneuron and muscle morphology following spinal cord injury. J Comp Neurol. 2012; 520(12):2683-96. PMC: 3960947. DOI: 10.1002/cne.23066. View

3.
Jessen K, Mirsky R . The repair Schwann cell and its function in regenerating nerves. J Physiol. 2016; 594(13):3521-31. PMC: 4929314. DOI: 10.1113/JP270874. View

4.
Zhang Y, Zheng S, Geng Y, Xue J, Wang Z, Xie X . MicroRNA profiling of atrial fibrillation in canines: miR-206 modulates intrinsic cardiac autonomic nerve remodeling by regulating SOD1. PLoS One. 2015; 10(3):e0122674. PMC: 4376950. DOI: 10.1371/journal.pone.0122674. View

5.
Caiazzo M, Colucci-DAmato L, Esposito M, Parisi S, Stifani S, Ramirez F . Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages. Exp Cell Res. 2010; 316(14):2365-76. DOI: 10.1016/j.yexcr.2010.05.021. View