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Protease-activated receptor 2 (PAR2) is a central regulator of intestinal barrier function, inflammation and pain. Upregulated intestinal proteolysis and PAR2-signaling are implicated in inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS). To identify potential bacterial regulators of PAR2 activity, we developed a functional assay for PAR2 processing and used it to screen conditioned media from a library of diverse gut commensal microbes.
View Article and Find Full Text PDFInflammation and Coagulation in Neurologic and Psychiatric Disorders.
Semin Thromb Hemost
January 2025
Department of Neurology, Sheba Medical Center, Tel Ha'Shomer, Israel.
Coagulation factors are intrinsically expressed in various brain cells, including astrocytes and microglia. Their interaction with the inflammatory system is important for the well-being of the brain, but they are also crucial in the development of many diseases in the brain such as stroke and traumatic brain injury. The cellular effects of coagulation are mediated mainly by protease-activated receptors.
View Article and Find Full Text PDFBotulinum neurotoxins exploit host digestive proteases to boost their oral toxicity via activating OrfXs/P47.
Nat Struct Mol Biol
January 2025
Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Botulinum neurotoxins (BoNTs) rank among the most potent toxins and many of them are produced by bacteria carrying the orfX gene cluster that also encodes four nontoxic proteins (OrfX1, OrfX2, OrfX3 and P47). The orfX gene cluster is also found in the genomes of many non-BoNT-producing bacteria, often alongside genes encoding oral insecticidal toxins. However, the functions of these OrfXs and P47 remain elusive.
View Article and Find Full Text PDFProtease-activated receptor 1 in the pathogenesis of cystic fibrosis.
BMJ Open Respir Res
January 2025
Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Background: The most common cause of death in those with cystic fibrosis (CF) is respiratory failure due to bronchiectasis resulting from repeated cycles of respiratory infection and inflammation. Protease-activated receptor 1 (PAR1) is a cell surface receptor activated by serine proteases including neutrophil elastase, which is recognised as a potent modulator of inflammation. While PAR1 is known to play an important role in regulating inflammation, nothing is known about any potential role of this receptor in CF pathogenesis.
View Article and Find Full Text PDFNano-polymeric platinum activates PAR2 gene editing to suppress tumor metastasis.
Biomaterials
January 2025
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Beijing Institute of Technology Chongqing Innovation Center, Chongqing, 401120, China. Electronic address:
Metastasis as the hallmark of cancer preferentially contributes to tumor recurrence and therapy resistance, aggrandizing the lethality of patients with cancer. Despite their robust suppressions of tumor progression, chemotherapeutics failed to attenuate cancer cell migration and even triggered pro-metastatic effects. In parallel, protease-activated receptor 2 (PAR2), a member of the G protein-coupled receptor subfamily, actively participates in cancer metastasis via multiple signal transduction pathways.
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