Dataset Information

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

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.

SUBMITTER: Condorelli AG

PROVIDER: S-EPMC8106838 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Condorelli Angelo Giuseppe AG El Hachem May M Zambruno Giovanna G Nystrom Alexander A Candi Eleonora E Castiglia Daniele D

Journal of biomedical science 20210509 1

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 pr ...[more]

PMID: 33966637

Similar Datasets

Project description:Prevention and overcoming castration resistance of prostate cancer (PC) remains one of the main unsolved problems in modern oncology. Hence, many studies are focused on the investigation of novel androgen receptor (AR) regulators that could serve as potential drug targets in disease therapy. Among such factors, inhibitor of growth (ING) proteins were identified. Some ING proteins act as AR transcriptional coregulators, indicating their relevance for PC research. The ING family consists of five protein-coding genes from ING1 to ING5 and pseudogene INGX. The ING genes were revealed through their sequence homology to the first identified ING1 from an in vivo screen. ING factors are a part of histone modification complexes. With the help of the conserved plant homeodomain (PHD) motif, ING factors bind to Histone 3 Lysine 4 (H3K4) methylation mark with a stronger affinity to the highest methylation grade H3K4me3 and recruit histone acetyltransferases (HAT) and histone deacetylases (HDAC) to chromatin. ING1 and ING2 are core subunits of mSIN3a-HDAC corepressor complexes, whereas ING3-5 interact with different HAT complexes that serve as coactivators. ING members belong to type II tumour suppressors and are frequently downregulated in many types of malignancies, including PC. As the family name indicates, ING proteins are able to inhibit cell growth and tumour development via regulation of cell cycle and cancer-relevant pathways such as apoptosis, cellular senescence, DNA repair, cell migration, invasion, and angiogenesis. Many ING splice variants that enhance the diversity of ING activity were discovered. However, it seems that the existence of multiple ING splice variants is underestimated, since alternative splice variants, such as the AR coregulators ING1 and ING3, counteract full-length ING and thus play an opposite functional role. These results open a novel prospective investigation direction in understanding ING factors biology in PC and other malignancies.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets