Molecular Activation of the NLRP3 Inflammasome in Fibrosis: Common Threads Linking Divergent Fibrogenic Diseases
| Autor: | James D. Thacker, Carol M. Artlett |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Inflammasomes
Physiology Clinical Biochemistry Biochemistry Fibrosis NLR Family Pyrin Domain-Containing 3 Protein medicine Humans Autocrine signalling Lung Molecular Biology Skin General Environmental Science Calcium signaling NADPH oxidase biology NADPH Oxidases Inflammasome Cell Biology Endoplasmic Reticulum Stress medicine.disease Cell biology Immunology biology.protein General Earth and Planetary Sciences Calcium Signal transduction Carrier Proteins Reactive Oxygen Species Wound healing Myofibroblast medicine.drug |
| Zdroj: | Antioxidants & Redox Signaling. 22:1162-1175 |
| ISSN: | 1557-7716 1523-0864 |
| Popis: | Over the past 10 years, there has been a plethora of investigations centering on the NLRP3 inflammasome and its role in fibrosis and other disease pathologies. To date, the signaling pathways from the inflammasome to myofibroblast differentiation and chronic collagen synthesis have not been fully elucidated, and many questions are left to be answered.Recent studies have demonstrated the significant and critical role of reactive oxygen species (ROS) and calcium signaling in the assembly of the inflammasome, and this may result in autocrine signaling maintaining the myofibroblast phenotype, leading to fibrotic disease.Traditionally, myofibroblasts under tight regulation aid in wound healing and then, once the wound has closed, undergo apoptosis and the collagen in the wound remodels. During fibrosis, however, the myofibroblast maintains an activated state via a chronically activated inflammasome, leading to the continual synthesis of collagens and other extracellular matrix proteins that result in damage to the tissue or organ. The mechanism that is driving this abnormality has not been fully elucidated.However, studies have been conducted to suggest that modulating the calcium or the ROS axis may be of therapeutic value in regulating inflammasome activation. A number of novel drugs are currently being developed that may prove beneficial to patients suffering from fibrotic diseases. |
| Databáze: | OpenAIRE |
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