PMID- 31382189
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220526
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 17
DP  - 2019 Sep 6
TI  - Silencing of the MEKK2/MEKK3 Pathway Protects against Spinal Cord Injury via the 
      Hedgehog Pathway and the JNK Pathway.
PG  - 578-589
LID - S2162-2531(19)30144-1 [pii]
LID - 10.1016/j.omtn.2019.05.014 [doi]
AB  - Spinal cord injury (SCI) is a devastating medical condition, often accompanied by 
      motor and sensory dysfunction. The Hedgehog (Hh) pathway has a protective role in 
      pathological injury after SCI. However, the specific mechanism remains unclear. 
      The present study aimed to confirm the effects of the mitogen-activated protein 
      kinase kinase-2 (MEKK2)/MEKK3/JNK/Hh pathway on SCI. SCI rat models were 
      established and then inoculated with plasmids overexpressing MEKK2/MEKK3 or with 
      small interfering RNA (siRNA) against MEKK2/MEKK3. The expression of MEKK2 and -3 
      was detected in dorsal root ganglia (DRG) cells. The motor function of hindlimbs, 
      the expression of the c-Jun N-terminal kinase (JNK)- and Hh-pathway-related 
      genes, and the level of neurofilament-200 (NF-200) and glial fibrillary acidic 
      protein (GFAP) were measured. MEKK2 and -3 were expressed at a high level in DRG 
      cells. The silencing of MEKK2/MEKK3 in rats caused an increase in the expression 
      of glioma-associated oncogene homolog-1 (Gli-1), Nestin, smoothened (Smo), and 
      Sonic Hedgehog (Shh). The Basso, Beattie, and Bresnahan (BBB) rating and the 
      level of NF-200 protein also increased. However, the expression of monocyte 
      chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1beta (MIP-1beta), 
      MIP-3alpha, p-JNK/JNK, and p-c-Jun/c-Jun and the level of GFAP were reduced. 
      Downregulation of MEKK2/MEKK3 ameliorated the symptoms of SCI by promoting neural 
      progenitor cell differentiation via activating the Hh pathway and disrupting the 
      JNK pathway. The findings in this study reveal a potential biomarker for SCI 
      treatment.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kong, Yan-Long
AU  - Kong YL
AD  - Department of Orthopaedics, Fengxian Hospital Affiliated to Anhui University of 
      Science and Technology, 6600 Nanfeng Road, Shanghai 201499, People's Republic of 
      China.
FAU - Wang, Yi-Fei
AU  - Wang YF
AD  - Department of Orthopaedics, Fengxian Hospital Affiliated to Southern Medical 
      University, 6600 Nanfeng Road, Shanghai 201499, People's Republic of China.
FAU - Zhu, Zhong-Sheng
AU  - Zhu ZS
AD  - Department of Orthopaedics, Fengxian Hospital Affiliated to Southern Medical 
      University, 6600 Nanfeng Road, Shanghai 201499, People's Republic of China.
FAU - Deng, Zheng-Wei
AU  - Deng ZW
AD  - Graduate School, Shanghai University of Traditional Chinese Medicine, 1200 Cailun 
      Road, Shanghai 201203, People's Republic of China.
FAU - Chen, Jing
AU  - Chen J
AD  - Graduate School, Shanghai University of Traditional Chinese Medicine, 1200 Cailun 
      Road, Shanghai 201203, People's Republic of China.
FAU - Zhang, Dong
AU  - Zhang D
AD  - Department of Orthopaedics, Fengxian Hospital Affiliated to Southern Medical 
      University, 6600 Nanfeng Road, Shanghai 201499, People's Republic of China.
FAU - Jiang, Qun-Hua
AU  - Jiang QH
AD  - Department of Orthopaedics, Fengxian Hospital Affiliated to Southern Medical 
      University, 6600 Nanfeng Road, Shanghai 201499, People's Republic of China. 
      Electronic address: jff1969@126.com.
FAU - Zhao, Shi-Chang
AU  - Zhao SC
AD  - Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 
      200233, People's Republic of China. Electronic address: zhaoshichang0404@163.com.
FAU - Zhang, Ya-Dong
AU  - Zhang YD
AD  - Department of Orthopaedics, Fengxian Hospital Affiliated to Anhui University of 
      Science and Technology, 6600 Nanfeng Road, Shanghai 201499, People's Republic of 
      China; Department of Orthopaedics, Fengxian Hospital Affiliated to Southern 
      Medical University, 6600 Nanfeng Road, Shanghai 201499, People's Republic of 
      China. Electronic address: zhangyadong6@126.com.
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20190604
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
RIN - Mol Ther Nucleic Acids. 2022 May 10;28:600. PMID: 35615008
PMC - PMC6682310
OTO - NOTNLM
OT  - Hedgehog signaling pathway
OT  - JNK signaling pathway
OT  - MEKK2/MEKK3
OT  - neural progenitor cell differentiation
OT  - spinal cord injury
EDAT- 2019/08/06 06:00
MHDA- 2019/08/06 06:01
PMCR- 2019/06/04
CRDT- 2019/08/06 06:00
PHST- 2019/03/15 00:00 [received]
PHST- 2019/05/17 00:00 [accepted]
PHST- 2019/08/06 06:00 [pubmed]
PHST- 2019/08/06 06:01 [medline]
PHST- 2019/08/06 06:00 [entrez]
PHST- 2019/06/04 00:00 [pmc-release]
AID - S2162-2531(19)30144-1 [pii]
AID - 10.1016/j.omtn.2019.05.014 [doi]
PST - ppublish
SO  - Mol Ther Nucleic Acids. 2019 Sep 6;17:578-589. doi: 10.1016/j.omtn.2019.05.014. 
      Epub 2019 Jun 4.