Pyroptosis in acute pancreatitis and its therapeutic regulation

Mamun, Abdullah Al; Suchi, Suzia Aktar; Aziz, Abdul; Zaeem, Muhammad; Munir, Fahad; Wu, Yanqing; Xiao, Jian

doi:10.1007/s10495-022-01729-w

Cited by 31 publications

(27 citation statements)

References 134 publications

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“…5D). Afterward, GSDMD was identified as a downstream target gene of miR-10a-5p via the Starbase Web site and has been demonstrated to be upregulated in AP (32,33), and pyroptosis mediated by excessive and uncontrolled GSDMD is correlated to the progression of AP (11,34). The subsequent experiments proved the targeted binding of miR-10a-5p to GSDMD ( P < 0.01, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…miR-10a-5a expression levels were increased after silencing USP25 while decreased upon KLF4 overexpression. In addition, mounting studies have emphasized GSDMD -mediated pyroptosis in AP (11,34). Our data exhibited the binding of miR-10a-5p to GSDMD and the positive relationship of GSDMD with USP25 and KLF4 , suggesting that KLF4 upregulated GSDMD level via downregulating miR-10a-5p transcriptionally.…”

Section: Discussionmentioning

confidence: 99%

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Usp25 Upregulation Boosts GSDMD-Mediated Pyroptosis of Acinar Cells in Acute Pancreatitis

Liu

Zhang

2022

Shock

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Acute pancreatitis (AP) is an inflammation-associated disorder in the digestive system. Ubiquitin-specific peptidase 25 (USP25) can modulate inflammation in diseases. This study expounded on the role of USP25 in pyroptosis of acinar cells in AP. Acinar cells were treated with lipopolysaccharide (LPS) and caerulein (CRE) to induce AP. Afterward, the expression patterns of USP25, microRNA (miR)-10a-5p, and Krüppel-like factor 4 (KLF4) in acinar cells were examined. Then, acinar cell viability and levels of NLR family pyrin-domain containing 3 (NLRP3), cleaved caspase-1, cleaved N-terminal gasdermin D (GSDMD-N), interleukin (IL)-1β, and IL-18 were determined. We observed that USP25 was highly expressed in AP models, and silencing USP25 increased cell viability and inhibited pyroptosis of AP acinar cells. The bindings of USP25 to KLF4 and miR-10a-5p to KLF4 and the GSDMD 3′UTR sequence were validated. We found that USP25 binding to KLF4 inhibited ubiquitination degradation of KLF4, KLF4 transcriptionally decreased miR-10a-5p expression, and miR-10a-5p targeted GSDMD expression. Finally, rescue experiments proved that KLF4 overexpression or miR-10a-5p suppression enhanced pyroptosis of AP acinar cells. Overall, USP25 stabilized KLF4 expression through deubiquitination, limited miR-10a-5p expression, and increased GSDMD expression, finally promoting pyroptosis of acinar cells in AP.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Usp25 Upregulation Boosts GSDMD-Mediated Pyroptosis of Acinar Cells in Acute Pancreatitis

Liu

Zhang

2022

Shock

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“…There is sound evidence that genetic and pharmacologic inhibition of NLRP3 inflammasome activation and subsequent pyroptosis attenuates pancreatic acinar cell death, experimental pancreatic injury, and inflammatory reaction [ 40 ]. Previous study has found that activation of pyroptosis significantly aggravate AP, it might be associated with activating the NLRP3 inflammasome and promoting caspase-1 self-cleavage and maturation, accompany by release of IL-1β and IL-18 [ 41 ]. These studies indicate that the indispensable role of NLRP3 inflammasome activation in pyroptosis in AP has been confirmed.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of TRAF6 improves hyperlipidemic acute pancreatitis by alleviating pyroptosis in vitro and in vivo rat models

et al. 2023

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Objective Hypertriglyceridemia (HTG) is one of the common causes of acute pancreatitis (AP). Hyperlipidemic acute pancreatitis (HTG-AP) is associated with higher mortality owing to its tendency for greater severity and rapid progression. The purpose of this study was to explore the mechanism of involvement of tumor necrosis factor receptor-related factor 6 (TRAF6) in pyroptosis during HTG-AP. Methods The HTG environment was simulated with palmitic acid treatment in vitro and a high-fat diet in vivo. Cerulein was used to establish the HTG-AP model, followed by genetic and pharmacological inhibition of TRAF6. Pyroptosis activation, inflammatory reaction, and the interaction between TRAF6 and pyroptosis in HTG-AP were assessed. Results HTG was found to aggravate the development of pancreatitis, accompanied by increased pyroptosis and enhanced inflammatory response in HTG-AP models. Mechanistically, TRAF6 downregulation decreased the activation of pyroptosis in cerulein-induced HTG-AP. Conclusion Collectively, inhibition of TRAF6 improved HTG-AP and the associated inflammation by alleviating pyroptosis.

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“…In the process of pyroptosis, inflammasomes activate caspase-1 or caspase-11/4/5, which 10.3389/fncel.2022.1013450 then cleaves gasdermin D (GSDMD) and separates its N-terminal pore-forming domain (PFD). The oligomers of PFD bind to the cell membrane and form macropores on the membrane, resulting in cell swelling and membrane rupture (Al Mamun et al, 2022). Increasing evidence indicates that pyroptosis is involved in many diseases, including CNS injuries (Mi et al, 2022;Wu et al, 2022).…”

Section: Pyroptosismentioning

confidence: 99%

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

Tian

Mao

Zhang

2022

Front. Cell. Neurosci.

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Central nervous system (CNS) injuries, including traumatic brain injury (TBI), intracerebral hemorrhage (ICH) and ischemic stroke, are the most common cause of death and disability around the world. As the most common modification on ribonucleic acids (RNAs), N6-methyladenosine (m6A) modification has recently attracted great attentions due to its functions in determining the fate of RNAs through changes in splicing, translation, degradation and stability. A large number of studies have suggested that m6A modification played an important role in brain development and involved in many neurological disorders, particularly in CNS injuries. It has been proposed that m6A modification could improve neurological impairment, inhibit apoptosis, suppress inflammation, reduce pyroptosis and attenuate ferroptosis in CNS injuries via different molecules including phosphatase and tensin homolog (PTEN), NLR family pyrin domain containing 3 (NLRP3), B-cell lymphoma 2 (Bcl-2), glutathione peroxidase 4 (GPX4), and long non-coding RNA (lncRNA). Therefore, m6A modification showed great promise as potential targets in CNS injuries. In this article, we present a review highlighting the role of m6A modification in CNS injuries. Hence, on the basis of these properties and effects, m6A modification may be developed as therapeutic agents for CNS injury patients.

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Pyroptosis in acute pancreatitis and its therapeutic regulation

Cited by 31 publications

References 134 publications

Usp25 Upregulation Boosts GSDMD-Mediated Pyroptosis of Acinar Cells in Acute Pancreatitis

Usp25 Upregulation Boosts GSDMD-Mediated Pyroptosis of Acinar Cells in Acute Pancreatitis

Inhibition of TRAF6 improves hyperlipidemic acute pancreatitis by alleviating pyroptosis in vitro and in vivo rat models

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

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