Introduction: Systemic sclerosis (SSc) is a chronic debilitating disease characterized by vascular insufficiency, widespread fibrosis and immune activation. Current understanding of its pathophysiology remains incomplete, which translates into inefficient therapies. Notch signaling is a central player in the development of physiological and pathological fibrosis not only in general but also in the context of SSc and is most likely involved in the vascular dysfunction that characterizes the disease.
Areas covered: This review explores the role of the Notch pathway in the pathophysiology of SSc and the potential implications for the diagnosis, evaluation, and management of this yet incurable disease.
Expert opinion: Although major issues still exist about the comprehension of SSc and the design of effective treatments, the knowledge of the role of the Notch pathway in fibrogenesis and vascular biology has shed light and enthusiasm over the field. Drugs that target components of Notch signaling are currently in development including already some in clinical trials. As such, Notch may become a very important topic in the near future (considering both the pathophysiology and treatment perspectives), not only in the context of SSc but also in the vascular-dependent fibrotic processes present in a multitude of diseases.
Keywords: Angiogenesis; Notch signaling; Notch targeting therapies; endothelial dysfunction; endothelial-to-mesenchymal transition; fibroblast; fibrogenesis; systemic sclerosis.