PMID- 26134946
OWN - NLM
STAT- MEDLINE
DCOM- 20160412
LR  - 20181113
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 135
IP  - 11
DP  - 2015 Nov
TI  - Filamin A Mediates Wound Closure by Promoting Elastic Deformation and Maintenance 
      of Tension in the Collagen Matrix.
PG  - 2852-2861
LID - S0022-202X(15)41872-X [pii]
LID - 10.1038/jid.2015.251 [doi]
AB  - Cell-mediated remodeling and wound closure are critical for efficient wound 
      healing, but the contribution of actin-binding proteins to contraction of the 
      extracellular matrix is not defined. We examined the role of filamin A (FLNa), an 
      actin filament cross-linking protein, in wound contraction and maintenance of 
      matrix tension. Conditional deletion of FLNa in fibroblasts in mice was 
      associated with ~4 day delay of full-thickness skin wound contraction compared 
      with wild-type (WT) mice. We modeled the healing wound matrix using cultured 
      fibroblasts plated on grid-supported collagen gels that create lateral 
      boundaries, which are analogues to wound margins. In contrast to WT cells, FLNa 
      knockdown (KD) cells could not completely maintain tension when matrix compaction 
      was resisted by boundaries, which manifested as relaxed matrix tension. 
      Similarly, WT cells on cross-linked collagen, which requires higher levels of 
      sustained tension, exhibited approximately fivefold larger deformation fields and 
      approximately twofold greater fiber alignment compared with FLNa KD cells. 
      Maintenance of boundary-resisted tension markedly influenced the elongation of 
      cell extensions: in WT cells, the number (~50%) and length (~300%) of cell 
      extensions were greater than FLNa KD cells. We conclude that FLNa is required for 
      wound contraction, in part by enabling elastic deformation and maintenance of 
      tension in the matrix.
FAU - Mohammadi, Hamid
AU  - Mohammadi H
AD  - Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada. 
      Electronic address: hamid.mohammadi@utoronto.ca.
FAU - Pinto, Vanessa I
AU  - Pinto VI
AD  - Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada.
FAU - Wang, Yongqiang
AU  - Wang Y
AD  - Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada.
FAU - Hinz, Boris
AU  - Hinz B
AD  - Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada.
FAU - Janmey, Paul A
AU  - Janmey PA
AD  - Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, 
      Pennsylvania, USA.
FAU - McCulloch, Christopher A
AU  - McCulloch CA
AD  - Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada.
LA  - eng
GR  - R01 EB017753/EB/NIBIB NIH HHS/United States
GR  - MOP-11106/Canadian Institutes of Health Research/Canada
GR  - STP-53877/Canadian Institutes of Health Research/Canada
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150702
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Filamins)
RN  - 9007-34-5 (Collagen)
SB  - IM
CIN - J Invest Dermatol. 2015 Nov;135(11):2569-71. PMID: 26548489
MH  - Animals
MH  - Cells, Cultured
MH  - Collagen/metabolism
MH  - Disease Models, Animal
MH  - Elasticity
MH  - Extracellular Matrix/*metabolism
MH  - Fibroblasts/metabolism/physiology
MH  - Filamins/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Random Allocation
MH  - Tensile Strength/*physiology
MH  - Wound Healing/*physiology
MH  - Wounds and Injuries/*metabolism/pathology
PMC - PMC4890573
MID - NIHMS789604
COIS- CONFLICT OF INTEREST The authors state no conflict of interest.
EDAT- 2015/07/03 06:00
MHDA- 2016/04/14 06:00
PMCR- 2016/06/02
CRDT- 2015/07/03 06:00
PHST- 2015/02/24 00:00 [received]
PHST- 2015/05/29 00:00 [revised]
PHST- 2015/06/09 00:00 [accepted]
PHST- 2015/07/03 06:00 [entrez]
PHST- 2015/07/03 06:00 [pubmed]
PHST- 2016/04/14 06:00 [medline]
PHST- 2016/06/02 00:00 [pmc-release]
AID - S0022-202X(15)41872-X [pii]
AID - 10.1038/jid.2015.251 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2015 Nov;135(11):2852-2861. doi: 10.1038/jid.2015.251. Epub 
      2015 Jul 2.