Ontology highlight
ABSTRACT:
PROVIDER: PRJNA802316 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17841905_1.fastq.gz | Fastqsanger.gz | |||
| SRR17841905_2.fastq.gz | Fastqsanger.gz | |||
| SRR17841906_1.fastq.gz | Fastqsanger.gz | |||
| SRR17841906_2.fastq.gz | Fastqsanger.gz |
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Project description:It is widely acknowledged that gasdermin family proteins, which are known as the executors of pyroptosis, undergo protease-mediated cleavage prior to inducing pyroptosis. Here, we unexpectedly discovered a non-canonical form of pyroptosis mediated by full-length GSDME (FL-GSDME) without any proteolytic cleavage. Upon intense ultraviolet (UV) irradiation-triggered DNA damage, hyperactivation of nuclear PARP1 led to extensive formation of poly(ADP-ribose) (PAR) polymers and then release to the cytoplasm.These PAR polymers activate PARP5 to catalyze GSDME PARylation, resulted in a conformational change in GSDME that relieved autoinhibition imposed by its C terminus on the N terminus. On the other hand, intense UV irradiation boosted mitochondrial fission-dependent generation of mitochondrial reactive oxygen species (mito-ROS), further promoting cytochrome c-catalyzed peroxidation of cardiolipin. This lipid-ROS signal was then sensed by PARylated-GSDME and then induced oxidative oligomerization of GSDME, which facilitated FL-GSDME plasma membrane targeting for perforation, eventually inducing pyroptosis. Reagents that concurrently stimulate PARPs activity and lipid-ROS also induced sequential modifications i.e., PARylation and oxidation of FL-GSDME and synergistically promoted pyroptotic cell death. Overall, our findings elucidate a novel mechanism underlying cleavage-independent function of GSDME in executing cell demise, further enriching the paradigms and cognition of FL-GSDME-mediated non-canonical pyroptosis.
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Project description:GSDME (Gasdermin E) is a critical protein known for its role in pyroptosis, a form of programmed cell death associated with inflammation. We demonstrated that GSDME as a crucial mediator in muscle repair, particularly in the context of muscle damage induced by cardiotoxin (CTX). Specifically, we found that GSDME-controlled pyroptosis promotes muscle repair by coordinating the activities of tissue-resident macrophages and fibro-adipogenic progenitors (FAPs).
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Project description:GSDME (Gasdermin E) is a critical protein known for its role in pyroptosis, a form of programmed cell death associated with inflammation. We demonstrated that GSDME as a crucial mediator in muscle repair, particularly in the context of muscle damage induced by cardiotoxin (CTX). Specifically, we found that GSDME-controlled pyroptosis promotes muscle repair by coordinating the activities of tissue-resident macrophages and fibro-adipogenic progenitors (FAPs).
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Project description:To revealed the significant involvement of GSDME-mediated pyroptosis in the pathogenesis and development of ICI-LI
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Project description:Acute kidney injury(AKI) is associated with an increased risk of chronic kidney disease(CKD). There is still a lack of effective prevention for AKI-CKD transition. In the present study, we simultaneously explored the contribution of GSDMD and GSDME in folic acid (FA)-induced nephropathy, a model mimicking the essential components of the AKI-CKD transition. We found that blockage of both GSDMD and GSDME-mediated pyroptosis could have accumulative protection against FA-induced AKI-CKD transition. GSDME-mediated pyroptosis played a crucial role in tubular cell damage. GSDMD could exert important functions in infiltration of inflammatory cells and NETs formation. Pyroptotic tubular cells triggered NETs generation and macrophage polarization. NETs promoted macrophage-to-myofibroblast transition. Our results illustrated the orchestration of GSDMD and GSDME in AKI-CKD transition, providing new insights into the molecular mechanism for the clinical dilemma.
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