Sciatic nerve regeneration in KLF7-transfected acellular nerve allografts.
OBJECTIVE
Krüppel-like Factor 7 (KLF7) is a transcription factor that promotes axon regeneration in the central nervous system. Here, we assessed whether KLF7 stimulates regeneration after peripheral nerve injury.


METHODS
C57BL/6 mice received an acellular nerve allograft (ANA) injected with either adeno-associated virus 2 (AAV2) vector or AAV2-KLF7 for sciatic nerve gap repair. After 4 weeks, KLF7 was detected by RT-PCR, western blot and immunohistochemistry in regenerated nerves. Axonal regeneration and functional recovery were examined by immunohistochemistry, Fluorogold (FG) and cholera toxin B (CTB) retrograde neural tracing, sciatic function index (SFI), angle of ankle, Hargreaves test and electrophysiological analysis.


RESULTS
With AAV2-KLF7 injection, KLF7 expression increased in regenerated nerves, and amplitude, score of SFI, angle of ankle and FG-labelled spinal cord neurons were increased. We observed elevated CTB-labelled neurons in dorsal root ganglia (DRG), neurofilaments, P0 (peripheral myelin) and S100 and decreased latency period and withdrawal latencies in the Hargreaves test. The SFI was significantly correlated with amplitude and regenerated axon number. Tyrosine kinase A (TrkA) and B (TrkB) receptors were also increased in the DRG.


CONCLUSIONS
Our findings suggest that KLF7 promoted peripheral nerve axonal regeneration, further supporting a role for KLF7 as a growth-promoting transcription factor in the injured nervous system.
a Department of Anatomy, Mudanjiang College of Medicine , Mudanjiang College of Medicine , Mudanjiang , China.
Ying
Y
Wang
a Department of Anatomy, Mudanjiang College of Medicine , Mudanjiang College of Medicine , Mudanjiang , China.
Wen-Yuan
WY
Li
a Department of Anatomy, Mudanjiang College of Medicine , Mudanjiang College of Medicine , Mudanjiang , China.
Ping
P
Sun
a Department of Anatomy, Mudanjiang College of Medicine , Mudanjiang College of Medicine , Mudanjiang , China.
Zai-Shun
ZS
Jin
a Department of Anatomy, Mudanjiang College of Medicine , Mudanjiang College of Medicine , Mudanjiang , China.
Gui-Bo
GB
Liu
b Stark Neurosciences Research Institute , Indiana University School of Medicine , Indianapolis , USA.
Ling-Xiao
LX
Deng
c Department of Pharmacy , Mudanjiang College of Medicine , Tongxiang Road, Aimin District, Mudanjiang 157011 , Heilongjiang , China.
Li-Xin
LX
Guan
D064591:Allografts / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002772:Cholera Toxin / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018993:Myelin P0 Protein / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000473:pathology / Q000601:surgery*; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors; D014161:Transduction, Genetic
D005904:Glial Fibrillary Acidic Protein; C426008:Klf7 protein, mouse; D051741:Kruppel-Like Transcription Factors; D018993:Myelin P0 Protein; D064568:S100 Calcium Binding Protein beta Subunit; D002772:Cholera Toxin
Acellular nerve allograft; Axonal regeneration; Fluorogold (FG); KLF7; Krüppel-like Factor 7 (KLF7); Peripheral nerve injury; acellular nerve allograft (ANA); adeno-associated virus 2 (AAV2); central nervous system (CNS); cholera toxin B (CTB); day (d); dorsal root ganglia (DRG); electroneurogram (ENG); glial fibrillary acidic proteins (GFAP); neurofilaments (NF); peripheral nervous system (PNS); sciatic function index (SFI); small proline-rich repeat protein 1A (SPRR1A); tyrosine kinase A (TrkA)