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Molecular Activation of the NLRP3 Inflammasome in Fibrosis: Common Threads Linking Divergent Fibrogenic Diseases
Journal article   Peer reviewed

Molecular Activation of the NLRP3 Inflammasome in Fibrosis: Common Threads Linking Divergent Fibrogenic Diseases

Carol M. Artlett and James D. Thacker
Antioxidants & redox signaling, v 22(13), pp 1162-1175
01 May 2015
PMID: 25329971

Abstract

Biochemistry & Molecular Biology Endocrinology & Metabolism Life Sciences & Biomedicine Science & Technology
Significance: 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 Advances: 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. Critical Issues: 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. Future Directions: 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. Antioxid. Redox Signal. 22, 1162-1175.

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Web of Science research areas
Biochemistry & Molecular Biology
Endocrinology & Metabolism
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