PMID- 27822714 OWN - NLM STAT- MEDLINE DCOM- 20190508 LR - 20210707 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 54 IP - 9 DP - 2017 Nov TI - TWEAK-Fn14 Influences Neurogenesis Status via Modulating NF-kappaB in Mice with Spinal Cord Injury. PG - 7497-7506 LID - 10.1007/s12035-016-0248-x [doi] AB - The aim of our research is to investigate the regulatory role of TNF-like weak inducer of apoptosis- fibroblast growth factor-inducible 14 (TWEAK-Fn14) pathway in nuclear factor-kappa B (NF-kappaB) expression and neurogenesis status after spinal cord injury (SCI). We constructed a mice model of spinal cord injury and injected different lentiviral vectors which were transfected with TWEAK, TWEAK small interfering RNA (siRNA) and Fn14 siRNA into different groups of mice. Locomotor functional recovery status of the hind limb in mice was assessed using the Basso, Beattie and Bresnahan (BBB) test. Apoptosis status in the injured area was examined via TDT-mediated dUTP-biotin nick end-labeling (TUNEL) staining, the expression of GAP-43 in injured spinal cord was quantified by immunohistochemistry and expressions of TWEAK, Fn14, NF-kappaB, TNF-alpha, and IL-1beta were evaluated by either western blot or ELISA. The expressions of TWEAK, Fn14, and NF-kappaB in the model group were significantly higher compared with those in the control group. Furthermore, the TWEAK group in which TWEAK was overexpressed exhibited significantly higher expressions of TWEAK, Fn14, and NF-kappaB, TNF-alpha and IL-1beta in relation to those in the model group (P < 0.05 for all). Moreover, the transfection of Fn14 siRNA antagonized the above effect of TWEAK transfection on injured mice. On the other hand, the TWEAK siRNA group in which the expression of TWEAK was inhibited exhibited significantly lower expressions of TWEAK, Fn14, NF-kappaB, TNF-alpha, and IL-1beta (P < 0.05 for all). Moreover, the transfection of TWEAK siRNA enhanced the locomotor functional recovery status in injured mice and suppressed the apoptosis of injured areas (P < 0.05 for all). In conclusion, stimulating the TWEAK-Fn14 pathway may elevate the expression of NF-kappaB, thereby slow the function recovery of SCI mice whereas inhibiting the TWEAK-Fn14 pathway may improve the neurogenesis status in mice with spinal cord injuries. FAU - Xu, Jing AU - Xu J AD - Department of Otolaryngology-Head and Neck Surgery, Xiang-Ya Hospital, Central South University, Changsha, Hunan, 410008, China. AD - Otolaryngology Key Laboratory of Hunan Province, Changsha, Hunan, 410008, China. FAU - He, Jian AU - He J AD - Department of Otolaryngology-Head and Neck Surgery, Xiang-Ya Hospital, Central South University, Changsha, Hunan, 410008, China. AD - Otolaryngology Key Laboratory of Hunan Province, Changsha, Hunan, 410008, China. FAU - He, Huang AU - He H AD - Department of Neurosurgery, Xiang-Ya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China. FAU - Peng, Renjun AU - Peng R AD - Department of Neurosurgery, Xiang-Ya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China. FAU - Xi, Jian AU - Xi J AD - Department of Neurosurgery, Xiang-Ya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China. dr_shiqing@163.com. LA - eng GR - 81201740/National Natural Science Foundation of China/International GR - 2012FJ6075/Program Sponsored by the Science and Technology Department of Hunan Province/International PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Retracted Publication DEP - 20161107 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (NF-kappa B) RN - 0 (TWEAK Receptor) SB - IM RIN - Mol Neurobiol. 2021 Jul;58(7):3601. PMID: 33991321 MH - Animals MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/*physiology MH - Neurogenesis/*physiology MH - Spinal Cord Injuries/*metabolism/pathology MH - TWEAK Receptor/antagonists & inhibitors/*biosynthesis OTO - NOTNLM OT - Fn14 OT - Gap-43 OT - NF-kappaB OT - Spinal cord injury (SCI) OT - Tweak EDAT- 2016/11/09 06:00 MHDA- 2019/05/09 06:00 CRDT- 2016/11/09 06:00 PHST- 2016/09/12 00:00 [received] PHST- 2016/10/23 00:00 [accepted] PHST- 2016/11/09 06:00 [pubmed] PHST- 2019/05/09 06:00 [medline] PHST- 2016/11/09 06:00 [entrez] AID - 10.1007/s12035-016-0248-x [pii] AID - 10.1007/s12035-016-0248-x [doi] PST - ppublish SO - Mol Neurobiol. 2017 Nov;54(9):7497-7506. doi: 10.1007/s12035-016-0248-x. Epub 2016 Nov 7.