Notch-ing up knowledge on molecular mechanisms of skin fibrosis: focus on the multifaceted Notch signalling pathway

Autor: Angelo Giuseppe Condorelli, May El Hachem, Giovanna Zambruno, Alexander Nystrom, Eleonora Candi, Daniele Castiglia
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Biomedical Science, Vol 28, Iss 1, Pp 1-17 (2021)
Druh dokumentu: article
ISSN: 1423-0127
DOI: 10.1186/s12929-021-00732-8
Popis: Abstract Fibrosis can be defined as an excessive and deregulated deposition of extracellular matrix proteins, causing loss of physiological architecture and dysfunction of different tissues and organs. In the skin, fibrosis represents the hallmark of several acquired (e.g. systemic sclerosis and hypertrophic scars) and inherited (i.e. dystrophic epidermolysis bullosa) diseases. A complex series of interactions among a variety of cellular types and a wide range of molecular players drive the fibrogenic process, often in a context-dependent manner. However, the pathogenetic mechanisms leading to skin fibrosis are not completely elucidated. In this scenario, an increasing body of evidence has recently disclosed the involvement of Notch signalling cascade in fibrosis of the skin and other organs. Despite its apparent simplicity, Notch represents one of the most multifaceted, strictly regulated and intricate pathways with still unknown features both in health and disease conditions. Starting from the most recent advances in Notch activation and regulation, this review focuses on the pro-fibrotic function of Notch pathway in fibroproliferative skin disorders describing molecular networks, interplay with other pro-fibrotic molecules and pathways, including the transforming growth factor-β1, and therapeutic strategies under development.
Databáze: Directory of Open Access Journals