Altered dynamics of transforming growth factor β (TGF-β) receptors in scleroderma fibroblasts. Issue 2 (15th November 2010)

• Record Type: Journal Article
• Authors: Asano, Yoshihide; Ihn, Hironobu; Jinnin, Masatoshi; Tamaki, Kunihiko; Sato, Shinichi
• Is Part Of: Annals of the rheumatic diseases. Volume 70:Issue 2(2011)
• Page Start: 384
• Page End: 387
• Publication Date: 2010-11-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2009.127811
• Languages: English
• ISSNs: 0003-4967

Abstract

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.