Upregulation of Thrombospondin 1 Expression in Synovial Tissues and Plasma of Rheumatoid Arthritis: Role of Transforming Growth Factor-β1 toward Fibroblast-like Synovial Cells

Objective.To investigate the role of thrombospondin 1 (TSP-1) in RA.Methods.Expression of TSP-1 in synovial tissues was determined by immunohistochemistry. Expression of TSP-1 in rheumatoid fibroblast-like synovial cells (FLS) was investigated by quantitative real-time PCR and ELISA. Correlations among the plasma TSP-1 and other variables in patients with RA were examined.Results.Expression of TSP-1 was increased in rheumatoid synovial tissues. Transforming growth factor-β1 (TGF-β1) clearly increased TSP-1 expression in FLS on both mRNA and protein levels. Changes in plasma TSP-1 were associated with those in 28-joint Disease Activity Score-erythrocyte sedimentation rate and plasma TGF-β1.Conclusion.TSP-1 might be critically involved in the disease process of RA through the TGF-β1/TSP-1 axis.

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Upregulation of Thrombospondin 1 Expression in Synovial Tissues and Plasma of Rheumatoid Arthritis: Role of Transforming Growth Factor-β1 toward Fibroblast-like Synovial Cells

The Journal of Rheumatology ◽

10.3899/jrheum.141292.c1 ◽

2017 ◽

Vol 44 (1) ◽

pp. 131-131 ◽

Cited By ~ 1

Keyword(s):

Rheumatoid Arthritis ◽

Growth Factor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Synovial Cells ◽

Thrombospondin 1 ◽

Synovial Tissues

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Thrombospondin-1 is not the major activator of TGF-β1 in thrombopoietin-induced myelofibrosis

Blood ◽

10.1182/blood-2010-07-294447 ◽

2011 ◽

Vol 117 (1) ◽

pp. 246-249 ◽

Cited By ~ 12

Author(s):

Solène Evrard ◽

Olivier Bluteau ◽

Micheline Tulliez ◽

Philippe Rameau ◽

Patrick Gonin ◽

...

Keyword(s):

Bone Marrow ◽

Growth Factor ◽

Transforming Growth Factor ◽

Active Form ◽

Transforming Growth Factor Β1 ◽

Myeloproliferative Syndrome ◽

Thrombospondin 1 ◽

Tgf Β1 ◽

Important Cytokine

Abstract Transforming growth factor-β1 (TGF-β1) is the most important cytokine involved in the promotion of myelofibrosis. Mechanisms leading to its local activation in the bone marrow environment remain unclear. As a recent study has highlighted the role of thrombospondin-1 (TSP-1) in platelet-derived TGF-β1 activation, we investigated the role of TSP-1 in the TPOhigh murine model of myelofibrosis. Two groups of engrafted mice, WT TPOhigh and Tsp-1–null TPOhigh, were constituted. All mice developed a similar myeloproliferative syndrome and an increase in total TGF-β1 levels in the plasma and in extracellular fluids of marrow and spleen. Surprisingly, we were able to detect the active form of TGF-β1 in Tsp-1–null TPOhigh mice. Accordingly, these mice developed marrow and spleen fibrosis, with intriguingly a higher grade than in WT TPOhigh mice. Our results show that TSP-1 is not the major activator of TGF-β1 in TPO-induced myelofibrosis, suggesting the contribution of another mechanism in the megakaryocyte/platelet compartment.

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