The α4β1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotype in dermal fibroblasts

Arti V. Shinde, Rhiannon Kelsh, John H. Peters, Kiyotoshi Sekiguchi, Livingston Van De Water, Paula J. McKeown-Longo

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Prompt deposition of fibronectin-rich extracellular matrix is a critical feature of normal development and the host-response to injury. Fibronectin isoforms that include the EDA and EDB domains are prominent in these fibronectin matrices. We now report using human dermal fibroblast cultures that the EDA domain of fibronectin or EDA-derived peptides modeled after the C-C' loop promote stress fiber formation and myosin-light chain phosphorylation. These changes are accompanied by an increase in fibronectin synthesis and fibrillogenesis. These effects are blocked by pretreating cells with either siRNA or blocking antibody to the α4 integrin. Our data indicate that the interaction between the α4β1 integrin and the EDA domain of fibronectin helps to drive tissue fibrosis by promoting a contractile phenotype and an increase in fibronectin synthesis and deposition.

Original languageEnglish (US)
Pages (from-to)26-35
Number of pages10
JournalMatrix Biology
Volume41
DOIs
StatePublished - Jan 1 2015

Fingerprint

Fibronectins
Integrins
Fibroblasts
Phenotype
Skin
Stress Fibers
Myosin Light Chains
Blocking Antibodies
Small Interfering RNA
Extracellular Matrix
Protein Isoforms
Fibrosis
Phosphorylation
Peptides
Wounds and Injuries

Keywords

  • Contractility
  • Fibronectin
  • Fibrosis
  • Rho kinase
  • Stress fibers
  • α4β1 integrin

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Shinde, A. V., Kelsh, R., Peters, J. H., Sekiguchi, K., Van De Water, L., & McKeown-Longo, P. J. (2015). The α4β1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotype in dermal fibroblasts. Matrix Biology, 41, 26-35. https://doi.org/10.1016/j.matbio.2014.11.004

The α4β1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotype in dermal fibroblasts. / Shinde, Arti V.; Kelsh, Rhiannon; Peters, John H.; Sekiguchi, Kiyotoshi; Van De Water, Livingston; McKeown-Longo, Paula J.

In: Matrix Biology, Vol. 41, 01.01.2015, p. 26-35.

Research output: Contribution to journalArticle

Shinde, AV, Kelsh, R, Peters, JH, Sekiguchi, K, Van De Water, L & McKeown-Longo, PJ 2015, 'The α4β1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotype in dermal fibroblasts', Matrix Biology, vol. 41, pp. 26-35. https://doi.org/10.1016/j.matbio.2014.11.004
Shinde, Arti V. ; Kelsh, Rhiannon ; Peters, John H. ; Sekiguchi, Kiyotoshi ; Van De Water, Livingston ; McKeown-Longo, Paula J. / The α4β1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotype in dermal fibroblasts. In: Matrix Biology. 2015 ; Vol. 41. pp. 26-35.
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