Endogenous tRNA‐derived small RNA (tRF3‐Thr‐AGT) inhibits ZBP1/NLRP3 pathway‐mediated cell pyroptosis to attenuate acute pancreatitis (AP)

Sun, Boshi; Chen, Zhuomiaoyu; Chi, Qiang; Zhang, Yifan; Gao, Bo

doi:10.1111/jcmm.16972

Cited by 17 publications

(9 citation statements)

References 54 publications

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Section: Zbp1 Signaling In Auto-inflammatory Diseasesmentioning

confidence: 99%

“…Moreover, the uncontrolled expression of ZBP1 and following ZBP1-dependent pyroptosis are the main reason for acute pancreatitis (AP) [ 170 ]. The tRF3-THr-AGT, an endogenous tRNA-derived small RNAs (tsRNAs), specifically binds the 3’ untranslated regions (3’-UTR) of ZBP1 mRNA to form short dsRNA that causes the degradation of ZBP1 mRNA [ 170 ]. In the cellular and animal AP models, the tRF3-THr-AGT is aberrantly decreased resulting in the upregulation of ZBP1, the activation of ZBP1-mediated NLRP3 inflammasome, and the extracellular release of cytokines and DAMPs [ 170 , 171 ].…”

Section: Zbp1 Signaling In Auto-inflammatory Diseasesmentioning

confidence: 99%

“…The tRF3-THr-AGT, an endogenous tRNA-derived small RNAs (tsRNAs), specifically binds the 3’ untranslated regions (3’-UTR) of ZBP1 mRNA to form short dsRNA that causes the degradation of ZBP1 mRNA [ 170 ]. In the cellular and animal AP models, the tRF3-THr-AGT is aberrantly decreased resulting in the upregulation of ZBP1, the activation of ZBP1-mediated NLRP3 inflammasome, and the extracellular release of cytokines and DAMPs [ 170 , 171 ]. In addition, further verification is needed to affirm whether the upregulated ZBP1 mediates apoptosis or necroptosis in acinar cells to aggravate AP.…”

Section: Zbp1 Signaling In Auto-inflammatory Diseasesmentioning

confidence: 99%

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ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity

Hao

Yang

et al. 2022

IJMS

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Z-conformation nucleic acid binding protein 1 (ZBP1), a powerful innate immune sensor, has been identified as the important signaling initiation factor in innate immune response and the multiple inflammatory cell death known as PANoptosis. The initiation of ZBP1 signaling requires recognition of left-handed double-helix Z-nucleic acid (includes Z-DNA and Z-RNA) and subsequent signaling transduction depends on the interaction between ZBP1 and its adapter proteins, such as TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1), and RIPK3. ZBP1 activated innate immunity, including type-I interferon (IFN-I) response and NF-κB signaling, constitutes an important line of defense against pathogenic infection. In addition, ZBP1-mediated PANoptosis is a double-edged sword in anti-infection, auto-inflammatory diseases, and tumor immunity. ZBP1-mediated PANoptosis is beneficial for eliminating infected cells and tumor cells, but abnormal or excessive PANoptosis can lead to a strong inflammatory response that is harmful to the host. Thus, pathogens and host have each developed multiplex tactics targeting ZBP1 signaling to maintain strong virulence or immune homeostasis. In this paper, we reviewed the mechanisms of ZBP1 signaling, the effects of ZBP1 signaling on host immunity and pathogen infection, and various antagonistic strategies of host and pathogen against ZBP1. We also discuss existent gaps regarding ZBP1 signaling and forecast potential directions for future research.

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Section: Zbp1 Signaling In Auto-inflammatory Diseasesmentioning

confidence: 99%

Section: Zbp1 Signaling In Auto-inflammatory Diseasesmentioning

confidence: 99%

Section: Zbp1 Signaling In Auto-inflammatory Diseasesmentioning

confidence: 99%

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ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity

Hao

Yang

et al. 2022

IJMS

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“…Downregulated tRF3-Thr-AGT was shown to be involved in pancreatic acinar intracellular trypsinogen activation (PAITA), which is an important event in the early stage of acute pancreatitis (AP) ( Yang et al, 2022 ). In addition, tRF3-Thr-AGT has been proven to restrain NLRP3-mediated pyroptotic cell death and inflammation in AP models by suppressing ZBP1 expression ( Sun et al, 2021 ). However, there are currently no reports on tRF3-Thr-CGT, and this survey shows that genes affected by this tRNA isodecoder pool may be involved in the pathological process of addiction.…”

Section: Discussionmentioning

confidence: 99%

Differential expression profiling of tRNA-Derived small RNAs and their potential roles in methamphetamine self-administered rats

Zhou

Hong

et al. 2023

Front. Genet.

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Transfer RNA-derived small RNAs (tsRNAs) are a novel class of short, non-coding RNAs that are closely associated with the pathogenesis of various diseases. Accumulating evidence has demonstrated their critical functional roles as regulatory factors in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress. However, the underlying mechanisms by which tRFs & tiRNAs affect methamphetamine-induced pathophysiological processes are largely unknown. In this study, we used a combination of small RNA sequencing, quantitative reverse transcription-polymerase chain reaction (qRT‒PCR), bioinformatics, and luciferase reporter assays to screen the expression profiles and identify the functional roles of tRFs and tiRNAs in the nucleus accumbens (NAc) of methamphetamine self-administration rat models. A total of 461 tRFs & tiRNAs were identified in the NAc of rats after 14 days of methamphetamine self-administration training. Of those, 132 tRFs & tiRNAs were significantly differentially expressed: 59 were significantly upregulated, whereas 73 were significantly downregulated in the rats with methamphetamine self-administration. Decreased expression levels of tiRNA-1-34-Lys-CTT-1 and tRF-1-32-Gly-GCC-2-M2, as well as increased expression levels of tRF-1-16-Ala-TGC-4 in the METH group compared with the saline control were validated by using RT‒PCR. Then, bioinformatic analysis was performed to analyse the possible biological functions of tRFs & tiRNAs in methamphetamine-induced pathogenesis. Furthermore, tRF-1-32-Gly-GCC-2-M2 was identified to target BDNF using the luciferase reporter assay. An altered tsRNA expression pattern was proven, and tRF-1-32-Gly-GCC-2-M2 was shown to be involved in methamphetamine-induced pathophysiologic processes by targeting BDNF. The current study provides new insights for future investigations to explore the mechanisms and therapeutic methods for methamphetamine addiction.

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“…The rat pancreatitis model was induced by 5% sodium taurocholate (1 mL/kg; Sigma, USA) according to the protocols provided previously with minor changes [ 39 ]. A total of 14 rats were evenly and randomly divided into two groups.…”

Section: Methodsmentioning

confidence: 99%

Keratin 8 Is an Inflammation-Induced and Prognosis-Related Marker for Pancreatic Adenocarcinoma

et al. 2022

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Pancreatic ductal adenocarcinoma (PDAC) is one of the highest-grade malignancies in the world. More effective biomarkers and treatment plans are necessary to improve the diagnosis rate and clinical outcome. The oncogenesis of PDAC is influenced by several factors, including chronic pancreatitis (CP). Keratin 8 (KRT8) is an important member of the keratin protein family and plays a role in regulating the cellular response to stress stimuli and mediating inflammatory reactions. However, the role of KRT8 in pancreatitis and PDAC is still poorly understood. Here we assessed the differentially expressed genes (DEGs) by bioinformatic methods with expression profiles available online for a caerulein-induced mouse model and human PDAC tissue. The prognostic value was evaluated by Kaplan–Meier analysis and Cox regression analysis. The diagnostic value was evaluated by Receiver Operating Characteristic analysis (ROC). The function of the genes was predicted by protein-protein interaction analysis, correlation analysis, and GO analysis. The conclusion was further validated in rat pancreatitis model, human tissue, and PDAC cell lines, including immunohistochemical staining (IHC), CCK-8 assay, wound healing assay, and flow cytometry. KRT8 was found to be upregulated in murine pancreatitis tissue, human CP tissue, and human PDAC tissue. High expression of KRT8 had a negative impact on the prognosis of PDAC patients. KRT8 was predicted to be involved in the regulation of the migration and viability of PDAC cells, which was validated in PDAC cell lines. Knockdown of KRT8 impaired the migration and proliferation and induced apoptosis in PDAC cell lines. In conclusion, keratin 8 is an inflammation-induced molecule and could serve as a diagnostic and prognostic marker for PDAC patients. More studies are needed for further validation from the perspective of precision and individualized medicine.

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Endogenous tRNA‐derived small RNA (tRF3‐Thr‐AGT) inhibits ZBP1/NLRP3 pathway‐mediated cell pyroptosis to attenuate acute pancreatitis (AP)

Cited by 17 publications

References 54 publications

ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity

ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity

Differential expression profiling of tRNA-Derived small RNAs and their potential roles in methamphetamine self-administered rats

Keratin 8 Is an Inflammation-Induced and Prognosis-Related Marker for Pancreatic Adenocarcinoma

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