Open AccessDeletion of Krüppel-like factor-4 promotes axonal regeneration in mammals
Author(s) -
Jinhui Xu,
XuZhen Qin,
Haonan Zhang,
Yanxia Ma,
ShiBin Qi,
Hongcheng Zhang,
Jinjin Ma,
Xinya Fu,
Jile Xie,
Saijilafu
Publication year - 2021
Publication title -
neural regeneration research/neural regeneration research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.286978
Subject(s) - regeneration (biology) , dorsal root ganglion , neuroscience , sciatic nerve , knockout mouse , klf4 , biology , corticospinal tract , axotomy , anatomy , spinal cord , microbiology and biotechnology , central nervous system , medicine , induced pluripotent stem cell , embryonic stem cell , biochemistry , receptor , radiology , gene , diffusion mri , magnetic resonance imaging
Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01).