Inhibition of KLF7-Targeting Micro RNA 146b Promotes Sciatic Nerve Regeneration

【Author】

Wen-Yuan Li;Wei-Ting Zhang;Yong-Xia Cheng;Yan-Cui Liu;Feng-Guo Zhai;Ping Sun;Hui-Ting Li;Ling-Xiao Deng;Xiao-Feng Zhu;Ying Wang;Department of Anatomy, Mudanjiang College of Medicine;The Affiliated Hongqi Hospital, Mudanjiang College of Medicine;Department of Pathology, Mudanjiang College of Medicine;Department of Pharmacy, Mudanjiang College of Medicine;Spinal Cord and Brain Injury Research Group, Stark Neuro-sciences Research Institute, Indiana University School of Medicine;

【Institution】

Department of Anatomy, Mudanjiang College of Medicine;The Affiliated Hongqi Hospital, Mudanjiang College of Medicine;Department of Pathology, Mudanjiang College of Medicine;Department of Pharmacy, Mudanjiang College of Medicine;Spinal Cord and Brain Injury Research Group, Stark Neuro-sciences Research Institute, Indiana University School of Medicine;

【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 micro RNA-146 b(mi R-146 b)affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with mi RNA lentivirus, mi RNA inhibitor lentivirus, or KLF7 si RNA lentivirus in vitro. The expression of mi R146 b 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 mi R-146 b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. mi R-146 b directly targeted KLF7 by binding to the 30-UTR, suppressing KLF7. Up-regulation of mi R-146 b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing mi R-146 b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which mi R-146 b was expressed in vivo.Similarly, 4 weeks after the ANA, anti-mi R-146 b 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 mi R-146 b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.

【Keywords】

miR-146b;;KLF7;;Schwann cells;;Sciatic nerve injury

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Total: 48 articles

  • [1] Ying Wang;Wen-Yuan Li;Zhi-Gang Li;Li-Xin Guan;Ling-Xiao Deng;Department of Anatomy,Mudanjiang College of Medicine;Department of General Surgery,First Affiliated Hospital of Mudanjiang College of Medicine;Department of Pharmacy,Mudanjiang College of Medicine;Spinal Cord and Brain Injury Research Group,Stark Neurosciences Research Institute,Indiana University School of Medicine;, Transcriptional and Epigenetic Regulation in Injury-Mediated Neuronal Dendritic Plasticity, Neuroscience Bulletin,
  • [2] Xiaojian Jia;Feng Wang;Ying Han;Xuewen Geng;Minghua Li;Yu Shi;Lin Lu;Yun Chen;Shenzhen Key Laboratory for Drug Addiction and Medication Safety,Department of Ultrasound,Peking University Shenzhen Hospital,Biomedical Research Institute,Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center;Department of Physiology and Neurobiology,Xinxiang Medical University;Institute of Mental Health,Peking University Sixth Hospital and Key Laboratory of Mental Health,National Institute on Drug Dependence,Peking University;, miR-137 and miR-491 Negatively Regulate Dopamine Transporter Expression and Function in Neural Cells, Neuroscience Bulletin,
  • [3] Massimiliano Caiazzo;;Luca Colucci-D'Amato;;Maria T. Esposito;;Silvia Parisi;;Stefano Stifani;;Francesco Ramirez;;Umberto di Porzio, Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages, Experimental Cell Research,
  • [4] Matthew B. Veldman;;Michael A. Bemben;;Robert C. Thompson;;Daniel Goldman, Gene expression analysis of zebrafish retinal ganglion cells during optic nerve regeneration identifies KLF6a and KLF7a as important regulators of axon regeneration, Developmental Biology,

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