Research ArticleFibrosis

Epigenetic activation and memory at a TGFB2 enhancer in systemic sclerosis

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Science Translational Medicine  19 Jun 2019:
Vol. 11, Issue 497, eaaw0790
DOI: 10.1126/scitranslmed.aaw0790

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An epigenetic sclerotic lock

Systemic sclerosis (SSc) is an autoimmune disease resulting in progressive fibrosis of connective tissue for which few therapies are available. Shin et al. found an enhancer whose epigenetic activation led to sustained up-regulation of TGFB2, but not other isoforms of TGFB, in fibroblasts from patients with diffuse SSc. Constitutive activation of TGFβ2 signaling in patient fibroblasts resulted from NF-κB and BRD4 occupancy at the enhancer. Accordingly, treatment with the bromodomain inhibitor JQ1 repressed collagen synthesis and reversed fibrosis in patient skin explants. TGFβ2 signaling may thus be a key, potentially targetable mechanism of fibrosis in some patients with diffuse SSc.

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