Fibroblast abnormalities in the pathogenesis of systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a chronic systemic disease characterized by autoimmunity, vascular lesions and progressive fibrosis. The fibrotic component is dominant in SSc compared with other vascular or autoimmune diseases and determines its prognosis and therapeutic refractoriness. Fibroblasts are responsible for abnormal extracellular matrix accumulation. Studies in cultured SSc skin fibroblasts have facilitated the identification of potential pathways involved in their profibrotic phenotype. Profibrotic fibroblasts characterized by abnormal growth and extracellular matrix synthesis may differentiate or expand from normal resident fibroblasts. Recruitment of bone marrow-derived progenitors and transdifferentiation of different cell lineages might also be involved. Multiple factors and signaling pathways appear to be involved in the development or persistence of the SSc fibroblast phenotype. Although their relative relevance and interplay are unclear, aberrant TGF-β signaling seems pivotal and constitutes the best characterized therapeutic target.

Keywords::

• collagen synthesis
• fibroblasts
• fibrosis
• SMAD
• systemic sclerosis
• TGF-β

Acknowledgements

The authors thank Gabriel Criado for critical reading of this manuscript.

Financial & competing interests disclosure

The authors’ research is supported by the Fondo de Investigación Santitaria del ISCIII PI 08/0316 (Spain). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.