The Significance of NOTCH Pathway in the Development of Fibrosis in Systemic Sclerosis

Szymon Zmorzyński; Wojciech Styk; Agata Anna Filip; Dorota Krasowska

doi:10.5021/ad.2019.31.4.365

The Significance of NOTCH Pathway in the Development of Fibrosis in Systemic Sclerosis

Ann Dermatol. 2019 Aug;31(4):365-371. doi: 10.5021/ad.2019.31.4.365. Epub 2019 Jul 1.

Authors

Szymon Zmorzyński¹, Wojciech Styk¹, Agata Anna Filip¹, Dorota Krasowska²

Affiliations

¹ Department of Cancer Genetics with Cytogenetic Laboratory, Medical University of Lublin, Poland.
² Chair and Department of Dermatology, Venerology and Paediatric Dermatology, Medical University of Lublin, Poland.

Abstract

Systemic sclerosis (SSc) is an autoimmune disorder characterized by the fibrosis of skin, heart, lung, and kidney as well. Excessive activation of fibroblasts is associated with higher expression of Notch1 and/or Notch3 genes. The constitutive expression of NOTCH genes was described in epithelial cells: epidermal keratinocytes, hair follicle cells and sebaceous glands. The NOTCH signalling pathway may be involved in the development of fibrosis, myofibroblast formation and the process of epithelial-mesenchymal transition. Activation of the NOTCH pathway leads to morphological, phenotypic and functional changes in epithelial cells. Furthermore, inhibition of Notch signalling prevent the development of fibrosis in different models, among them, bleomycin-induced fibrosis and in the Task-1 mause model. Molecular mechanisms, including the role of NOTCH signaling pathway, associated with fibrosis in SSc have not been completely recognized.

Keywords: Fibrosis; NOTCH genes; NOTCH pathway; Scleroderma; Transforming growth factor beta; systemic.

Publication types

Review