PMID- 27427941
OWN - NLM
STAT- MEDLINE
DCOM- 20170726
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 7
DP  - 2016
TI  - The Influence of Differentially Expressed Tissue-Type Plasminogen Activator in 
      Experimental Autoimmune Encephalomyelitis: Implications for Multiple Sclerosis.
PG  - e0158653
LID - 10.1371/journal.pone.0158653 [doi]
LID - e0158653
AB  - Tissue type plasminogen activator (t-PA) has been implicated in the development 
      of multiple sclerosis (MS) and in rodent models of experimental autoimmune 
      encephalomyelitis (EAE). We show that levels of t-PA mRNA and activity are 
      increased ~4 fold in the spinal cords of wild-type mice that are mice subjected 
      to EAE. This was also accompanied with a significant increase in the levels of 
      pro-matrix metalloproteinase 9 (pro-MMP-9) and an influx of fibrinogen. We next 
      compared EAE severity in wild-type mice, t-PA-/- mice and T4+ transgenic mice 
      that selectively over-express (~14-fold) mouse t-PA in neurons of the central 
      nervous system. Our results confirm that t-PA deficient mice have an earlier 
      onset and more severe form of EAE. T4+ mice, despite expressing higher levels of 
      endogenous t-PA, manifested a similar rate of onset and neurological severity of 
      EAE. Levels of proMMP-9, and extravasated fibrinogen in spinal cord extracts were 
      increased in mice following EAE onset regardless of the absence or 
      over-expression of t-PA wild-type. Interestingly, MMP-2 levels also increased in 
      spinal cord extracts of T4+ mice following EAE, but not in the other genotypes. 
      Hence, while the absence of t-PA confers a more deleterious form of EAE, neuronal 
      over-expression of t-PA does not overtly protect against this condition with 
      regards to symptom onset or severity of EAE.
FAU - Dahl, Lisa Cm
AU  - Dahl LC
AD  - Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, 
      Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia.
FAU - Nasa, Zeyad
AU  - Nasa Z
AD  - Department of Immunology, Central Clinical School, Monash University, Melbourne, 
      VIC, 3004, Australia.
FAU - Chung, JieYu
AU  - Chung J
AD  - Department of Immunology, Central Clinical School, Monash University, Melbourne, 
      VIC, 3004, Australia.
FAU - Niego, Be'eri
AU  - Niego B
AD  - Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, 
      Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia.
FAU - Tarlac, Volga
AU  - Tarlac V
AD  - Van Cleef Roet Centre for Nervous Diseases, Central Clinical School, Monash 
      University, Melbourne, VIC, 3004, Australia.
FAU - Ho, Heidi
AU  - Ho H
AD  - Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, 
      Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia.
FAU - Galle, Adam
AU  - Galle A
AD  - Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, 
      Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia.
FAU - Petratos, Steven
AU  - Petratos S
AD  - Department of Medicine, Central Clinical School, Monash University, Melbourne, 
      3004, Victoria, Australia.
FAU - Lee, Jae Young
AU  - Lee JY
AD  - Department of Medicine, Central Clinical School, Monash University, Melbourne, 
      3004, Victoria, Australia.
FAU - Alderuccio, Frank
AU  - Alderuccio F
AD  - Department of Immunology, Central Clinical School, Monash University, Melbourne, 
      VIC, 3004, Australia.
FAU - Medcalf, Robert L
AU  - Medcalf RL
AD  - Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, 
      Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia.
LA  - eng
PT  - Journal Article
DEP - 20160718
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 9001-32-5 (Fibrinogen)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Encephalomyelitis, Autoimmune, Experimental/*genetics/metabolism/pathology
MH  - Fibrinogen/analysis/metabolism
MH  - Gene Deletion
MH  - Male
MH  - Matrix Metalloproteinase 9/analysis/metabolism
MH  - Mice, Inbred C57BL
MH  - Multiple Sclerosis/*genetics/metabolism/pathology
MH  - Spinal Cord/metabolism/pathology
MH  - Tissue Plasminogen Activator/analysis/*genetics/metabolism
MH  - Up-Regulation
PMC - PMC4948890
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/07/20 06:00
MHDA- 2017/07/27 06:00
PMCR- 2016/07/18
CRDT- 2016/07/19 06:00
PHST- 2015/12/09 00:00 [received]
PHST- 2016/06/17 00:00 [accepted]
PHST- 2016/07/19 06:00 [entrez]
PHST- 2016/07/20 06:00 [pubmed]
PHST- 2017/07/27 06:00 [medline]
PHST- 2016/07/18 00:00 [pmc-release]
AID - PONE-D-15-53417 [pii]
AID - 10.1371/journal.pone.0158653 [doi]
PST - epublish
SO  - PLoS One. 2016 Jul 18;11(7):e0158653. doi: 10.1371/journal.pone.0158653. 
      eCollection 2016.