Evaluation of ATF3 in systemic sclerosis and fibrotic diseases

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The hallmark of systemic sclerosis (SSc) is progressive fibrosis of the skin and internal organs accompanied by the abnormal activation of the immune system, vasculopathy, and a high risk of mortality. Despite the great medical need, anti-fibrotic therapies are not yet available for clinical use. The chronic activity of transforming growth factor (TGF)-b resulting in activation of fibroblasts and excessive accumulation of extracellular matrix is characteristic for SSc and other fibrotic diseases. The molecular mechanisms behind are still unknown. Activating transcription factor (ATF)3 might be an important factor in the pro-fibrotic signaling of TGF-b, since ATF3 is activated by TGF-b and involved in inflammation, tissue repair and vascular homeostasis. However, its function and regulation in fibrotic disorders are not understood yet. This project aims to investigate the role of ATF3 in the pathogenesis of fibrotic diseases.