Document Detail


Fibroblast cytoskeletal remodeling contributes to connective tissue tension.
MedLine Citation:
PMID:  20945345     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The visco-elastic behavior of connective tissue is generally attributed to the material properties of the extracellular matrix rather than cellular activity. We have previously shown that fibroblasts within areolar connective tissue exhibit dynamic cytoskeletal remodeling within minutes in response to tissue stretch ex vivo and in vivo. Here, we tested the hypothesis that fibroblasts, through this cytoskeletal remodeling, actively contribute to the visco-elastic behavior of the whole tissue. We measured significantly increased tissue tension when cellular function was broadly inhibited by sodium azide and when cytoskeletal dynamics were compromised by disrupting microtubules (with colchicine) or actomyosin contractility (via Rho kinase inhibition). These treatments led to a decrease in cell body cross-sectional area and cell field perimeter (obtained by joining the end of all of a fibroblast's processes). Suppressing lamellipodia formation by inhibiting Rac-1 decreased cell body cross-sectional area but did not affect cell field perimeter or tissue tension. Thus, by changing shape, fibroblasts can dynamically modulate the visco-elastic behavior of areolar connective tissue through Rho-dependent cytoskeletal mechanisms. These results have broad implications for our understanding of the dynamic interplay of forces between fibroblasts and their surrounding matrix, as well as for the neural, vascular, and immune cell populations residing within connective tissue.
Authors:
Helene M Langevin; Nicole A Bouffard; James R Fox; Bradley M Palmer; Junru Wu; James C Iatridis; William D Barnes; Gary J Badger; Alan K Howe
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  226     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-02-22     Completed Date:  2011-04-14     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1166-75     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Wiley-Liss, Inc.
Affiliation:
Department of Neurology, University of Vermont, Burlington, Vermont 05405, USA. helene.langevin@uvm.edu
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MeSH Terms
Descriptor/Qualifier:
Amides / pharmacology
Animals
Cell Shape
Colchicine / pharmacology
Connective Tissue / drug effects,  metabolism*
Cytoskeleton / drug effects,  metabolism*
Elasticity
Fibroblasts / drug effects,  metabolism*
Male
Mice
Mice, Inbred C57BL
Neuropeptides / antagonists & inhibitors,  metabolism
Protein Kinase Inhibitors / pharmacology
Pseudopodia / drug effects,  metabolism
Pyridines / pharmacology
Sodium Azide / pharmacology
Stress, Mechanical
Time Factors
Tubulin Modulators / pharmacology
rac GTP-Binding Proteins / antagonists & inhibitors,  metabolism
rho-Associated Kinases / antagonists & inhibitors,  metabolism
Grant Support
ID/Acronym/Agency:
R01 AR051146/AR/NIAMS NIH HHS; R01 AR051146-05/AR/NIAMS NIH HHS; R01 AR051146-06/AR/NIAMS NIH HHS; R01 AR051146-08/AR/NIAMS NIH HHS; R01 AT001121-09/AT/NCCAM NIH HHS; R01 AT001121-10/AT/NCCAM NIH HHS; R01 GM074204/GM/NIGMS NIH HHS; R01 GM097495/GM/NIGMS NIH HHS; R01-AT001121/AT/NCCAM NIH HHS
Chemical
Reg. No./Substance:
0/Amides; 0/Neuropeptides; 0/Protein Kinase Inhibitors; 0/Pyridines; 0/Rac1 protein, mouse; 0/Tubulin Modulators; 138381-45-0/Y 27632; 26628-22-8/Sodium Azide; 64-86-8/Colchicine; EC 2.7.11.1/rho-Associated Kinases; EC 3.6.5.2/rac GTP-Binding Proteins
Comments/Corrections

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