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J Orthop Translat 2021 May 17;28:100-107. Epub 2021 Mar 17.

Center for Translational Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.

Background: The Notch signalling pathway has been reported to play a key role in rheumatoid arthritis (RA) development. Thus, inhibition of the activation of this signalling pathway may be a promising approach to the treatment of RA. In this study, the Notch signalling inhibitor LY411575, which can inhibit both Notch1 and Notch3, was used for the treatment of collagen-induced arthritis (CIA) rats. Read More

J Biol Chem 2021 Mar 26:100599. Epub 2021 Mar 26.

Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China. Electronic address:

Sphingosine-1-phosphate (S1P), a natural multifunctional phospholipid, is highly increased in plasma from patients with pulmonary arterial hypertension (PAH) and mediates proliferation of pulmonary artery smooth muscle cell (PASMC) by activating Notch3 signaling pathway. However, the mechanisms underpinning S1P-mediated induction of PASMC proliferation remain unclear. In this study, using biochemical and molecular biology approaches, RNA-interference and gene expression analyses, 5'-Ethynyl-2'-deoxyuridine (EdU) incorporation assay and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, we demonstrated that S1P promoted the activation of STAT3 through sphingosine-1-phosphate receptor 2 (S1PR2), and subsequently upregulated the expression of the microRNA miR-135b, which further reduced the expression of E3 ubiquitin ligase β-transduction repeat-containing protein (β-TrCP) and led to a reduction in YAP ubiquitinated degradation in PASMC. Read More

J Biol Chem 2021 Mar 25:100593. Epub 2021 Mar 25.

Faculty of Science and Engineering/ Cell Biology, Åbo Akademi University, Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland; Department of Biomedical Engineering, Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands. Electronic address:

Dysregulation of the developmentally important Notch signaling pathway is implicated in several types of cancer, including breast cancer. However, the specific roles and regulation of the four different Notch receptors have remained elusive. We have previously reported that the oncogenic PIM kinases phosphorylate Notch1 and Notch3. Read More

J Biol Chem 2021 Mar 24:100583. Epub 2021 Mar 24.

Departments of Orthopaedic Surgery,; the UConn Musculoskeletal Institute, UConn Health, Farmington, CT 06030.

Notch receptors maintain skeletal homeostasis. NOTCH1 and 2 have been studied for their effects on bone remodeling. Whereas NOTCH3 plays a significant role in vascular physiology, knowledge about its function in other cellular environments, including bone, is limited. Read More

Sci Rep 2021 Mar 25;11(1):6846. Epub 2021 Mar 25.

Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l`Hospital de la Santa Creu i Sant Pau, C/Sant Antoni María Claret 167, Barcelona, Spain.

CADASIL is a small vessel disease caused by mutations in NOTCH3 that lead to an odd number of cysteines in the EGF-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraine, psychiatric disturbances, recurrent strokes and dementia, being executive function characteristically impaired. The molecular pathways altered by this receptor aggregation need to be studied further. Read More