p21Cip1/WAF1 regulates radial axon growth and enhances motor functional recovery in the injured peripheral nervous system.
Recent studies have provided evidence that p21Cip1/WAF1 has not only cell cycle-associated activities but also other biological activities like neurite elongation. To investigate the role of p21Cip1/WAF1 in the in vivo axonal regeneration in the peripheral nervous system, we developed a p21Cip1/WAF1 knockout (KO) mice sciatic nerve injury model. We performed quantitative assessments of the functional, histological, and electrophysiological recoveries after sciatic nerve injury in p21Cip1/WAF1 KO mice and compared the results with those of the wild-type mice. p21Cip1/WAF1 KO mice showed a significant delay of the motor functional recovery between 21 and 42 days after sciatic nerve injury. The values of motor conduction velocity in p21Cip1/WAF1 KO mice were significantly lower than those in the wild-type mice on postoperative day 28. The mean percent neural tissue and the mean nerve axon width of p21Cip1/WAF1 KO mice were significantly less than those of the wild-type mice, which was caused by hyperphosphorylation of neurofilaments. Therefore, p21Cip1/WAF1 was considered to be involved in radial axon growth and to be essential for the motor functional recovery following peripheral nervous system injury.
Tomita
Koichi
K
Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 C11 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Kubo
Tateki
T
Matsuda
Ken
K
Madura
Tomas
T
Yano
Kenji
K
Fujiwara
Tatsuji
T
Tanaka
Hiroyuki
H
Tohyama
Masaya
M
Hosokawa
Ko
K
D000818:Animals; D000870:Anterior Horn Cells / Q000378:metabolism / Q000502:physiology*; D001369:Axons / Q000473:pathology / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000172:deficiency / Q000502:physiology*; D005727:Ganglia, Spinal / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009412:Nerve Fibers / Q000473:pathology; D009431:Neural Conduction / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020127:Recovery of Function / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D013997:Time Factors
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016900:Neurofilament Proteins; D012333:RNA, Messenger; C051774:neurofilament protein H