PMID- 32232913
OWN - NLM
STAT- MEDLINE
DCOM- 20210127
LR  - 20210127
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 34
IP  - 5
DP  - 2020 May
TI  - Overexpression of Rictor in the injured spinal cord promotes functional recovery 
      in a rat model of spinal cord injury.
PG  - 6984-6998
LID - 10.1096/fj.201903171R [doi]
AB  - Rictor is an essential component that directly activates the mammalian target of 
      rapamycin (mTOR) activity, which contributes to the intrinsic axon growth 
      capacity of adult sensory neurons after injury. However, whether its action also 
      applies to regeneration after spinal cord injury (SCI) remains unknown. In this 
      study, rats were given spinal cord contusion at the T9-10 level to establish the 
      SCI model and were subsequently treated with intraspinal cord injection of a 
      Rictor overexpression lentiviral vector to locally upregulate the Rictor 
      expression in the injured spinal cord. Thereafter, we investigated the 
      therapeutic effects of Rictor overexpression in the injured spinal cords of SCI 
      rats. Rictor overexpression not only significantly attenuated the acute 
      inflammatory response and cell death after SCI but also markedly increased the 
      shift in macrophages around the lesion from the M1 to M2 phenotype compared to 
      those of the control lentiviral vector injection-treated group. Furthermore, 
      Rictor overexpression dramatically increased neurogenesis in the lesion 
      epicenter, subsequently promoting the tissue repair and functional recovery in 
      SCI rats. Interestingly, the mechanism underlying the beneficial effects of 
      Rictor overexpression on SCI may be associated with the Rictor overexpression 
      playing a role in the anti-inflammatory response and driving macrophage 
      polarization toward the M2 phenotype, which benefits resident neuronal and 
      oligodendrocyte survival. Our findings demonstrate that Rictor is an effective 
      target that affects the generation of molecules that inhibit spinal cord 
      regeneration. In conclusion, localized Rictor overexpression represents a 
      promising potential strategy for the repair of SCI.
CI  - (c) 2020 The Authors. The FASEB Journal published by Wiley Periodicals Inc on 
      behalf of Federation of American Societies for Experimental Biology.
FAU - Chen, Ningning
AU  - Chen N
AD  - Department of Orthopedics, The Seventh Affiliated Hospital, Sun Yat-sen 
      University, Shenzhen, China.
FAU - Zhou, Pengxiang
AU  - Zhou P
AD  - Department of Physical Diagnostic, Daqing Longnan Hospital, Daqing, China.
FAU - Liu, Xizhe
AU  - Liu X
AD  - Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Li, Jiachun
AU  - Li J
AD  - Department of Orthopedics, The Seventh Affiliated Hospital, Sun Yat-sen 
      University, Shenzhen, China.
FAU - Wan, Yong
AU  - Wan Y
AD  - Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Liu, Shaoyu
AU  - Liu S
AD  - Department of Orthopedics, The Seventh Affiliated Hospital, Sun Yat-sen 
      University, Shenzhen, China.
FAU - Wei, Fuxin
AU  - Wei F
AD  - Department of Orthopedics, The Seventh Affiliated Hospital, Sun Yat-sen 
      University, Shenzhen, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200331
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (RICTOR protein, human)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (Recombinant Proteins)
RN  - 0 (rictor protein, rat)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Survival
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Macrophages/classification/metabolism/pathology
MH  - Motor Neurons/pathology/physiology
MH  - Neuronal Plasticity
MH  - Oligodendroglia/pathology/physiology
MH  - Rapamycin-Insensitive Companion of mTOR Protein/genetics/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/genetics/metabolism
MH  - Recovery of Function/genetics/physiology
MH  - Remyelination
MH  - Spinal Cord Injuries/pathology/physiopathology/*therapy
MH  - Up-Regulation
OTO - NOTNLM
OT  - Rictor
OT  - functional recovery
OT  - neurogenesis
OT  - spinal cord injury
EDAT- 2020/04/02 06:00
MHDA- 2021/01/28 06:00
CRDT- 2020/04/02 06:00
PHST- 2019/12/20 00:00 [received]
PHST- 2020/02/26 00:00 [revised]
PHST- 2020/03/17 00:00 [accepted]
PHST- 2020/04/02 06:00 [pubmed]
PHST- 2021/01/28 06:00 [medline]
PHST- 2020/04/02 06:00 [entrez]
AID - 10.1096/fj.201903171R [doi]
PST - ppublish
SO  - FASEB J. 2020 May;34(5):6984-6998. doi: 10.1096/fj.201903171R. Epub 2020 Mar 31.