Inhibition of KLF7-Targeting MicroRNA 146b Promotes Sciatic Nerve Regeneration.
10.1007/s12264-018-0206-x
- Author:
Wen-Yuan LI
1
;
Wei-Ting ZHANG
2
;
Yong-Xia CHENG
3
;
Yan-Cui LIU
1
;
Feng-Guo ZHAI
4
;
Ping SUN
1
;
Hui-Ting LI
2
;
Ling-Xiao DENG
5
;
Xiao-Feng ZHU
6
;
Ying WANG
7
Author Information
1. Department of Anatomy, Mudanjiang College of Medicine, Mudanjiang, 157011, China.
2. The Affiliated Hongqi Hospital, Mudanjiang College of Medicine, Mudanjiang, 157011, China.
3. Department of Pathology, Mudanjiang College of Medicine, Mudanjiang, 157011, China.
4. Department of Pharmacy, Mudanjiang College of Medicine, Mudanjiang, 157011, China.
5. Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
6. Department of Anatomy, Mudanjiang College of Medicine, Mudanjiang, 157011, China. sjkx@sohu.com.
7. Department of Anatomy, Mudanjiang College of Medicine, Mudanjiang, 157011, China. yingwang2016@sina.com.
- Publication Type:Journal Article
- Keywords:
KLF7;
Schwann cells;
Sciatic nerve injury;
miR-146b
- MeSH:
Animals;
Cell Movement;
genetics;
Cell Proliferation;
genetics;
Disease Models, Animal;
Female;
Ganglia, Spinal;
cytology;
Gene Expression Regulation;
genetics;
physiology;
HEK293 Cells;
Humans;
Kruppel-Like Transcription Factors;
genetics;
metabolism;
Male;
MicroRNAs;
genetics;
metabolism;
Motor Endplate;
genetics;
Myelin P0 Protein;
metabolism;
Nerve Regeneration;
genetics;
physiology;
Nerve Tissue Proteins;
metabolism;
RNA, Small Interfering;
genetics;
metabolism;
Rats;
Rats, Sprague-Dawley;
Rats, Wistar;
Sciatic Neuropathy;
metabolism;
surgery;
therapy
- From:
Neuroscience Bulletin
2018;34(3):419-437
- CountryChina
- Language:English
-
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.
