Research ArticleFibrosis

FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling

Science Translational Medicine  16 Apr 2014:
Vol. 6, Issue 232, pp. 232ra50
DOI: 10.1126/scitranslmed.3008264

You are currently viewing the editor's summary.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

Scleroderma Takes Its Toll

Scleroderma is a disease where the immune system attacks the connective tissues of the body, with notable hardening of the skin and fibrosis in multiple organs. However, what causes scleroderma—and the associated persistent fibrosis activation—remains unknown. Bhattacharyya et al. now report that the fibronectin extra domain A (FnEDA)—an endogenous damage-induced TLR4 ligand—may contribute to cutaneous fibrosis.

The authors found that FnEDA is elevated in lesions and circulation both of patients with scleroderma and of a mouse model of fibrosis. FnEDA was up-regulated by TGF-β in healthy fibroblasts. In vitro, FnEDA increased mechanical stiffness of human skin equivalents. Indeed, the profibrotic responses induced by FnEDA were dependent on TLR4 signaling and could be blocked by genetic, RNA interference, and pharmacologic TLR4 inhibition. These data suggest that a damage-induced TLR4 signaling may contribute to fibrogenesis in scleroderma.