PMID- 23625833
OWN - NLM
STAT- MEDLINE
DCOM- 20140210
LR  - 20220309
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 61
IP  - 7
DP  - 2013 Jul
TI  - NFATc3 promotes Ca(2+) -dependent MMP3 expression in astroglial cells.
PG  - 1052-66
LID - 10.1002/glia.22494 [doi]
AB  - Increase in intracellular calcium ([Ca(2+) ]i ) is a key mediator of astrocyte 
      signaling, important for activation of the calcineurin (CN)/nuclear factor of 
      activated T cells (NFAT) pathway, a central mediator of inflammatory events. We 
      analyzed the expression of matrix metalloproteinase 3 (Mmp3) in response to 
      increases in [Ca(2+) ]i and the role of the CN/NFAT pathway in this regulation. 
      Astrocyte Mmp3 expression was induced by overexpression of a constitutively 
      active form of NFATc3, whereas other MMPs and tissue inhibitor of 
      metalloproteinases (TIMP) were unaffected. Mmp3 mRNA and protein expression was 
      also induced by calcium ionophore (Io) and 2'(3')-O-(4-benzoylbenzoyl) adenosine 
      5'-triphosphate (Bz-ATP) and Mmp3 upregulation was prevented by the CN inhibitor 
      cyclosporin A (CsA). Ca(2+) -dependent astrocyte Mmp3 expression was also 
      inhibited by actinomycin D, and a Mmp3 promoter luciferase reporter was 
      efficiently activated by increased [Ca(2+) ]i , indicating regulation at the 
      transcriptional level. Furthermore, Ca(2+) /CN/NFAT dependent Mmp3 expression was 
      confirmed in pure astrocyte cultures derived from neural stem cells (Ast-NSC), 
      demonstrating that the induced Mmp3 expression occurs in astrocytes, and not 
      microglial cells. In an in vivo stab-wound model of brain injury, MMP3 expression 
      was detected in NFATc3-positive scar-forming astrocytes. Because [Ca(2+) ]i 
      increase is an early event in most brain injuries, these data support an 
      important role for Ca(2+) /CN/NFAT-induced astrocyte MMP3 expression in the early 
      neuroinflammatory response. Understanding the molecular pathways involved in this 
      regulation could provide novel therapeutic targets and approaches to promoting 
      recovery of the injured brain.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Neria, Fernando
AU  - Neria F
AD  - Unidad de Neuroinflamacion, Area de Biologia Celular y del Desarrollo, Unidad 
      Funcional de Investigacion en Enfermedades Cronicas, Instituto de Salud Carlos 
      III, Majadahonda, Madrid, Spain.
FAU - del Carmen Serrano-Perez, Maria
AU  - del Carmen Serrano-Perez M
FAU - Velasco, Patricia
AU  - Velasco P
FAU - Urso, Katia
AU  - Urso K
FAU - Tranque, Pedro
AU  - Tranque P
FAU - Cano, Eva
AU  - Cano E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130426
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (transcription factor NF-AT c3)
RN  - 37558-16-0 (Phorbol 12,13-Dibutyrate)
RN  - 4P5DXU1F8Q (3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/analogs & derivatives/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/drug effects/*metabolism
MH  - Brain/cytology
MH  - Calcium/*metabolism
MH  - Cerebral Cortex/metabolism/pathology
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/pharmacology
MH  - Flow Cytometry
MH  - Gene Expression Regulation/drug effects/genetics/*physiology
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NFATC Transcription Factors/genetics/*metabolism
MH  - Phorbol 12,13-Dibutyrate/pharmacology
MH  - Signal Transduction/drug effects/genetics
MH  - Time Factors
MH  - Wounds and Injuries/pathology
EDAT- 2013/04/30 06:00
MHDA- 2014/02/11 06:00
CRDT- 2013/04/30 06:00
PHST- 2012/10/09 00:00 [received]
PHST- 2013/02/14 00:00 [accepted]
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2014/02/11 06:00 [medline]
AID - 10.1002/glia.22494 [doi]
PST - ppublish
SO  - Glia. 2013 Jul;61(7):1052-66. doi: 10.1002/glia.22494. Epub 2013 Apr 26.