Affordable Access

deepdyve-link
Publisher Website

Physiological Fluid Flow Moderates Fibroblast Responses to TGF-β1.

Authors
  • Nithiananthan, Sadhvi1
  • Crawford, Aileen2
  • Knock, Johnathan Cooper3
  • Lambert, Daniel W1
  • Whawell, Simon A1
  • 1 Academic Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
  • 2 Academic Unit of Restorative Dentistry, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
  • 3 Department of Neuroscience, Academic Neurology Unit, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
Type
Published Article
Journal
Journal of Cellular Biochemistry
Publisher
Wiley (John Wiley & Sons)
Publication Date
Apr 01, 2017
Volume
118
Issue
4
Pages
878–890
Identifiers
DOI: 10.1002/jcb.25767
PMID: 27748539
Source
Medline
Keywords
License
Unknown

Abstract

Fibroblasts are the major cellular component of connective tissue and experience mechanical perturbations due to matrix remodelling and interstitial fluid movement. Transforming growth factor β1 (TGF-β1) can promote differentiation of fibroblasts in vitro to a contractile myofibroblastic phenotype characterised by the presence of α-smooth muscle actin (α-SMA) rich stress fibres. To study the role of mechanical stimulation in this process, we examined the response of primary human fibroblasts to physiological levels of fluid movement and its influence on fibroblast differentiation and responses to TGF-β1. We reported that in both oral and dermal fibroblasts, physiological levels of fluid flow induced widespread changes in gene expression compared to static cultures, including up-regulation of genes associated with TGFβ signalling and endocytosis. TGF-β1, activin A and markers of myofibroblast differentiation including α-SMA and collagen IA1 were also increased by flow but surprisingly the combination of flow and exogenous TGF-β1 resulted in reduced differentiation. Our findings suggest this may result from enhanced internalisation of caveolin and TGF-β receptor II. These findings suggest that a) low levels of fluid flow induce myofibroblast differentiation and b) fluid flow antagonises the fibroblast response to pro-differentiation signals such as TGF-β1. We propose that this may be a novel mechanism by which mechanical forces buffer responses to chemical signals in vivo, maintaining a context-specific fibroblast phenotype. J. Cell. Biochem. 118: 878-890, 2017. © 2016 Wiley Periodicals, Inc.

Report this publication

Statistics

Seen <100 times