Accumulating evidence highlights a central role of Nlrp3 (NOD-like receptor family pyrin domain containing three) inflammasomes in the pathogenesis of various degenerative and fibrotic diseases, including atherosclerosis, hypertension, cardiac remodelling, and end-stage organ diseases. The Nlrp3 inflammasome monomer is a multi-subunit protein, which consists of pattern recognition receptor Nlrp3, the adaptor protein ASC (apoptotic speck-like protein) and inactive pro-caspase-1.
Upon receiving various danger signals, or in diseases, inflammasomes are oligomerized to form a high-molecular-weight inflammasome complex, in which procaspase-1 is converted to its active form, caspase-1. Activation of caspase-1 leads to tissue inflammation via the production of various inflammatory cytokines including interleukin 1ß (IL1ß) and interleukin 18 (IL18), or danger molecules such as HMGB1 (high molecular weight group box 1). These canonical cytokine and inflammatory cell-mediated inflammatory responses can cause or exacerbate the tissue inflammation and injury, contributing to the development of various degenerative and fibrotic diseases.
Moreover, recent studies showed that instigation of inflammasomes may exert non-canonical actions that directly cause cell dysfunction or injury independent of actions mediated by inflammatory cytokines. This growing list of non-canonical actions includes pyroptosis (a specific form of cell death that combines characteristics of apoptotic and necrotic death pathways), lipid handling, cytoskeleton rearrangement, intercellular junction protein regulation, or direct regulation of protein synthesis, metabolism, or secretion. In this regard, it is imperative to know the precise roles and regulatory molecular mechanisms of Nlrp3 inflammasomes in various tissue injury and fibrogenic diseases, which may provide clinical implications in developing pharmacological interventions targeting these inflammasomes.
This Research Topic will welcome original research as well as review articles to discuss all molecular aspects of inflammasomes in tissue injury and fibrosis that relate to the following topics:
-Novel danger associated molecular patterns (DAMPs) that sense inflammasomes.
-Molecular mechanisms triggering activation of inflammasomes.
-Signalling pathways that upregulates or downregulate inflammasome components.
-The novel functions of caspase-1 and their substrates beyond IL1ß and IL18.
-Therapeutic potential of targeting inflammasomes.
Accumulating evidence highlights a central role of Nlrp3 (NOD-like receptor family pyrin domain containing three) inflammasomes in the pathogenesis of various degenerative and fibrotic diseases, including atherosclerosis, hypertension, cardiac remodelling, and end-stage organ diseases. The Nlrp3 inflammasome monomer is a multi-subunit protein, which consists of pattern recognition receptor Nlrp3, the adaptor protein ASC (apoptotic speck-like protein) and inactive pro-caspase-1.
Upon receiving various danger signals, or in diseases, inflammasomes are oligomerized to form a high-molecular-weight inflammasome complex, in which procaspase-1 is converted to its active form, caspase-1. Activation of caspase-1 leads to tissue inflammation via the production of various inflammatory cytokines including interleukin 1ß (IL1ß) and interleukin 18 (IL18), or danger molecules such as HMGB1 (high molecular weight group box 1). These canonical cytokine and inflammatory cell-mediated inflammatory responses can cause or exacerbate the tissue inflammation and injury, contributing to the development of various degenerative and fibrotic diseases.
Moreover, recent studies showed that instigation of inflammasomes may exert non-canonical actions that directly cause cell dysfunction or injury independent of actions mediated by inflammatory cytokines. This growing list of non-canonical actions includes pyroptosis (a specific form of cell death that combines characteristics of apoptotic and necrotic death pathways), lipid handling, cytoskeleton rearrangement, intercellular junction protein regulation, or direct regulation of protein synthesis, metabolism, or secretion. In this regard, it is imperative to know the precise roles and regulatory molecular mechanisms of Nlrp3 inflammasomes in various tissue injury and fibrogenic diseases, which may provide clinical implications in developing pharmacological interventions targeting these inflammasomes.
This Research Topic will welcome original research as well as review articles to discuss all molecular aspects of inflammasomes in tissue injury and fibrosis that relate to the following topics:
-Novel danger associated molecular patterns (DAMPs) that sense inflammasomes.
-Molecular mechanisms triggering activation of inflammasomes.
-Signalling pathways that upregulates or downregulate inflammasome components.
-The novel functions of caspase-1 and their substrates beyond IL1ß and IL18.
-Therapeutic potential of targeting inflammasomes.
