Systemic sclerosis (SSc) is a connective-tissue disease more frequent in women than in men. Genetics have been hypothesized to have a main role in disease susceptibility, but none of the genetic factors put forward is sufficient to induce the disease. Recently, exogenous factors and epigenetic modifications have been proposed to have a role in the determination of the disease phenotype. For example, fibrotic signal transduction pathways in SSc converge on DNA methylation and histone deacetylation at the FLI1 gene. In addition, regulation of the COL1A1 gene in fibroblasts involves transcription factors (hc-Krox, Sp1, Sp3) which upregulate COL1A1 transcriptional activity and provide evidence for a profibrotic role of hc-Krox. These findings provide novel insights into the epigenetic regulation of fibrosis. They may suggest that the drugs acting on epigenetic mechanisms may be useful as antifibrotic treatments in SSc. © 2009 John Wiley & Sons Ltd.

Epigenetics and Systemic Sclerosis / Guiducci, Serena; Cerinic, Marco Matucci. - STAMPA. - (2009), pp. 327-338. [10.1002/9780470743553.ch18]

Epigenetics and Systemic Sclerosis

GUIDUCCI, SERENA;MATUCCI CERINIC, MARCO
2009

Abstract

Systemic sclerosis (SSc) is a connective-tissue disease more frequent in women than in men. Genetics have been hypothesized to have a main role in disease susceptibility, but none of the genetic factors put forward is sufficient to induce the disease. Recently, exogenous factors and epigenetic modifications have been proposed to have a role in the determination of the disease phenotype. For example, fibrotic signal transduction pathways in SSc converge on DNA methylation and histone deacetylation at the FLI1 gene. In addition, regulation of the COL1A1 gene in fibroblasts involves transcription factors (hc-Krox, Sp1, Sp3) which upregulate COL1A1 transcriptional activity and provide evidence for a profibrotic role of hc-Krox. These findings provide novel insights into the epigenetic regulation of fibrosis. They may suggest that the drugs acting on epigenetic mechanisms may be useful as antifibrotic treatments in SSc. © 2009 John Wiley & Sons Ltd.
2009
9780470758618
9780470758618
The Epigenetics of Autoimmune Diseases
327
338
Guiducci, Serena; Cerinic, Marco Matucci
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1067015
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