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Altered dynamics of transforming growth factor β (TGF-β) receptors in scleroderma fibroblasts
  1. Yoshihide Asano1,
  2. Hironobu Ihn2,
  3. Masatoshi Jinnin2,
  4. Kunihiko Tamaki1,
  5. Shinichi Sato1
  1. 1Department of Dermatology, University of Tokyo, Tokyo, Japan
  2. 2Department of Dermatology & Plastic and Reconstructive Surgery, Kumamoto University, Kumamoto, Japan
  1. Correspondence to Dr Yoshihide Asano, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan; yasano-tky{at}umin.ac.jp

Abstract

Objectives To investigate the difference in the dynamics of transforming growth factor β (TGF-β) receptors between normal and scleroderma fibroblasts.

Methods The cell surface expression levels of TGF-β receptors were determined by biotinylation and immunoprecipitation assay. The dynamics of TGF-β receptors on the cell surface was determined by the reversible biotinylation assay. The subcellular localisation of TGF-β receptors was determined by immunoprecipitation using antibodies against clathrin and caveolin.

Results Although the total expression levels of TGF-β receptors were elevated in scleroderma fibroblasts compared with normal fibroblasts, there was no significant difference in the cell surface expression levels of TGF-β receptors between these two groups. However, the internalisation rate of TGF-β receptors was higher in scleroderma fibroblasts compared with normal fibroblasts. Furthermore, caveolin constitutively made a complex with TGF-β receptors, while the interaction of clathrin with TGF-β receptors was marginal in scleroderma fibroblasts.

Conclusions The dynamics of TGF-β receptors on the cell surface is accelerated in scleroderma fibroblasts. Considering that the activation state of TGF-β signalling is regulated by a balance between the clathrin-dependent internalisation and the lipid raft-caveolar internalisation, the accumulation of TGF-β receptors in caveolin-positive vesicles may result in the deceleration of caveolin-dependent internalisation and subsequently lead to the relative acceleration of clathrin-dependent internalisation.

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Footnotes

  • Ethics approval This study was conducted with the approval of the University of Tokyo.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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