PMID- 27407006
OWN - NLM
STAT- MEDLINE
DCOM- 20170908
LR  - 20171201
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 30
IP  - 10
DP  - 2016 Oct
TI  - Filamin A regulates the organization and remodeling of the pericellular collagen 
      matrix.
PG  - 3613-3627
AB  - Extracellular matrix remodeling by cell adhesion-related processes is critical 
      for proliferation and tissue homeostasis, but how adhesions and the cytoskeleton 
      interact to organize the pericellular matrix (PCM) is not understood. We examined 
      the role of the actin-binding protein, filamin A (FLNa), in pericellular collagen 
      remodeling. Compared with wild-type (WT), mice with fibroblast-specific deletion 
      of FLNa exhibited higher density but reduced organization of collagen fibers 
      after increased loading of the periodontal ligament for 2 wk. In cultured 
      fibroblasts, FLNa knockdown (KD) did not affect collagen mRNA, but after 24 h of 
      culture, FLNa WT cells exhibited  approximately 2-fold higher cell-surface collagen KD cells 
      and 13-fold higher levels of activated beta1 integrins. In FLNa WT cells, there was 
      3-fold more colocalization of talin with pericellular cleaved collagen than in 
      FLNa KD cells. MMP-9 mRNA and protein expression were >2-fold higher in FLNa KD 
      cells than in WT cells. Cathepsin B, which is necessary for intracellular 
      collagen digestion, was >3-fold higher in FLNa WT cells than in KD cells. FLNa WT 
      cells exhibited 2-fold more collagen phagocytosis than KD cells, which involved 
      the FLNa actin-binding domain. Evidently, FLNa regulates PCM remodeling through 
      its effects on degradation pathways that affect the abundance and organization of 
      collagen.-Mezawa, M., Pinto, V. I., Kazembe, M. P., Lee, W. S., McCulloch, C. A. 
      Filamin A regulates the organization and remodeling of the pericellular collagen 
      matrix.
CI  - (c) FASEB.
FAU - Mezawa, Masaru
AU  - Mezawa M
AD  - Department of Periodontology, Nihon University School of Dentistry at Matsudo, 
      Matsudo, Japan; and.
FAU - Pinto, Vanessa I
AU  - Pinto VI
AD  - Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, 
      Ontario, Canada.
FAU - Kazembe, Mwayi P
AU  - Kazembe MP
AD  - Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, 
      Ontario, Canada.
FAU - Lee, Wilson S
AU  - Lee WS
AD  - Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, 
      Ontario, Canada.
FAU - McCulloch, Christopher A
AU  - McCulloch CA
AD  - Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, 
      Ontario, Canada christopher.mcculloch@utoronto.ca.
LA  - eng
GR  - MOP-11106/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160712
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Filamins)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Cell Adhesion/*physiology
MH  - Cell Membrane/*metabolism
MH  - Cell Movement/physiology
MH  - Collagen/*metabolism
MH  - Cytoskeleton/*metabolism
MH  - Extracellular Matrix/*metabolism
MH  - Fibroblasts/metabolism
MH  - Filamins/*metabolism
MH  - Horses
OTO - NOTNLM
OT  - degradation
OT  - lysosomes
OT  - matrix metalloproteinases
OT  - phagocytosis
EDAT- 2016/07/14 06:00
MHDA- 2017/09/09 06:00
CRDT- 2016/07/14 06:00
PHST- 2016/03/14 00:00 [received]
PHST- 2016/07/05 00:00 [accepted]
PHST- 2016/07/14 06:00 [pubmed]
PHST- 2017/09/09 06:00 [medline]
PHST- 2016/07/14 06:00 [entrez]
AID - fj.201600354RR [pii]
AID - 10.1096/fj.201600354RR [doi]
PST - ppublish
SO  - FASEB J. 2016 Oct;30(10):3613-3627. doi: 10.1096/fj.201600354RR. Epub 2016 Jul 
      12.