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

作　　者：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 

机构地区：[1]Department of Anatomy, Mudanjiang College of Medicine [2]The Affiliated Hongqi Hospital, Mudanjiang College of Medicine [3]Department of Pathology, Mudanjiang College of Medicine [4]Department of Pharmacy, Mudanjiang College of Medicine [5]Spinal Cord and Brain Injury Research Group, Stark Neuro-sciences Research Institute, Indiana University School of Medicine

出　　处：《Neuroscience Bulletin》2018年第3期419-437,共19页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China (81371362, 81641125, and 81500629);the Scientific Research Foundation of Heilongjiang Province, China (LC2017040);the Science Fund of Heilongjiang Provincial Health and Family Planning Commission, China (2016357 and 2016385);the Basic Research Operating Expenses Program of Heilongjiang Provincial Universities, China (2017- KYYWFMY0661)

摘　　要：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.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.

关 键 词：miR-146b KLF7 Schwann cells Sciatic nerve injury 

分 类 号：R745[医药卫生—神经病学与精神病学]