PMID- 22056987
OWN - NLM
STAT- MEDLINE
DCOM- 20120223
LR  - 20220317
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 480
IP  - 7377
DP  - 2011 Nov 6
TI  - Sustained axon regeneration induced by co-deletion of PTEN and SOCS3.
PG  - 372-5
LID - 10.1038/nature10594 [doi]
AB  - A formidable challenge in neural repair in the adult central nervous system (CNS) 
      is the long distances that regenerating axons often need to travel in order to 
      reconnect with their targets. Thus, a sustained capacity for axon regeneration is 
      critical for achieving functional restoration. Although deletion of either 
      phosphatase and tensin homologue (PTEN), a negative regulator of mammalian target 
      of rapamycin (mTOR), or suppressor of cytokine signalling 3 (SOCS3), a negative 
      regulator of Janus kinase/signal transducers and activators of transcription 
      (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted 
      significant optic nerve regeneration, such regrowth tapered off around 2 weeks 
      after the crush injury. Here we show that, remarkably, simultaneous deletion of 
      both PTEN and SOCS3 enables robust and sustained axon regeneration. We further 
      show that PTEN and SOCS3 regulate two independent pathways that act 
      synergistically to promote enhanced axon regeneration. Gene expression analyses 
      suggest that double deletion not only results in the induction of many 
      growth-related genes, but also allows RGCs to maintain the expression of a 
      repertoire of genes at the physiological level after injury. Our results reveal 
      concurrent activation of mTOR and STAT3 pathways as key for sustaining 
      long-distance axon regeneration in adult CNS, a crucial step towards functional 
      recovery.
FAU - Sun, Fang
AU  - Sun F
AD  - F.M. Kirby Neurobiology Center, Children's Hospital, Department of Neurology, 
      Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
FAU - Park, Kevin K
AU  - Park KK
FAU - Belin, Stephane
AU  - Belin S
FAU - Wang, Dongqing
AU  - Wang D
FAU - Lu, Tao
AU  - Lu T
FAU - Chen, Gang
AU  - Chen G
FAU - Zhang, Kang
AU  - Zhang K
FAU - Yeung, Cecil
AU  - Yeung C
FAU - Feng, Guoping
AU  - Feng G
FAU - Yankner, Bruce A
AU  - Yankner BA
FAU - He, Zhigang
AU  - He Z
LA  - eng
SI  - GEO/GSE32309
GR  - R01 EY021526/EY/NEI NIH HHS/United States
GR  - R01 EY021374/EY/NEI NIH HHS/United States
GR  - R01 EY021526-01/EY/NEI NIH HHS/United States
GR  - R01 EY021342-01A1/EY/NEI NIH HHS/United States
GR  - R01 EY018660/EY/NEI NIH HHS/United States
GR  - DP1 AG044161/AG/NIA NIH HHS/United States
GR  - R01 EY021342/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111106
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
SB  - IM
MH  - Animals
MH  - Axons/pathology/*physiology
MH  - Cell Growth Processes/genetics
MH  - Gene Expression Regulation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Crush
MH  - Nerve Regeneration/*physiology
MH  - Optic Nerve/cytology/growth & development/pathology
MH  - Optic Nerve Injuries/genetics/metabolism/pathology
MH  - PTEN Phosphohydrolase/*deficiency/genetics
MH  - Retinal Ganglion Cells/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins/*deficiency/genetics
PMC - PMC3240702
MID - NIHMS328231
COIS- Author information The authors declare no competing financial interests
EDAT- 2011/11/08 06:00
MHDA- 2012/02/24 06:00
PMCR- 2012/06/15
CRDT- 2011/11/08 06:00
PHST- 2011/06/01 00:00 [received]
PHST- 2011/09/28 00:00 [accepted]
PHST- 2011/11/08 06:00 [entrez]
PHST- 2011/11/08 06:00 [pubmed]
PHST- 2012/02/24 06:00 [medline]
PHST- 2012/06/15 00:00 [pmc-release]
AID - nature10594 [pii]
AID - 10.1038/nature10594 [doi]
PST - epublish
SO  - Nature. 2011 Nov 6;480(7377):372-5. doi: 10.1038/nature10594.