MicroRNA-122a aggravates intestinal ischemia/reperfusion injury by promoting pyroptosis via targeting EGFR-NLRP3 signaling pathway. 2022

Fei Wang, and Lidan Gu, and Yilin Wang, and Deen Sun, and Yuanhang Zhao, and Qiang Meng, and Lianhong Yin, and Lina Xu, and Xiaolong Lu, and Jinyong Peng, and Yuan Lin, and Pengyuan Sun
Department of Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, China.

Multiple studies have confirmed the significance of microRNA (miR)-122a in disease regulation. However, its impact on ischaemia/reperfusion (I/R) injury is unknown. In this study, we propose that the promoting role of miR-122a exists in I/R injuries. Two models, including hypoxia/reoxygenation (H/R)-injured IEC-6 cells in vitro and ischemia/reperfusion (I/R)-injured C57BL/6 mice intestinal tissues in vivo, were used to verify our purpose. Applying dual-luciferase reporter assays and transfection tests, the regulatory impacts of miR-122a were examined by promoting pyroptosis on intestinal I/R injury via targeting epidermal growth factor receptor (EGFR)-NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) signaling pathway. Both H/R-injured IEC-6 cells and I/R-injured mice intestinal tissues had elevated miR-122a expression, which targeted EGFR directly. Increased miR-122a expression significantly inhibited EGFR activity, decreased EGFR mRNA and protein expression, increased NLRP3 mRNA and protein expression, and up-regulated caspase 1, N-GSDMD, ASC, IL-1β, and IL-18 protein expression to promote pyroptosis. Furthermore, in IEC-6 cells, a miR-122a inhibitor and an EGFR-overexpression plasmid significantly reduced pyroptosis and alleviated intestinal I/R injury via activating the EGFR-NLRP3 signaling pathway, showing that miR-122a is very essential for regulating intestinal I/R injury. In brief, miR-122a promotes pyroptosis by inhibiting the EGFR-NLRP3 signaling pathway, which should be evaluated as a therapeutic target for intestinal I/R injury.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D000069292 Pyroptosis Type of programmed cell death associated with infection by intracellular pathogens. It is characterized by INFLAMMASOME formation; activation of CASPASE 1; and CYTOKINES mediated inflammation. Caspase-1 Dependent Cell Death,Inflammatory Apoptosis,Pyroptotic Cell Death,Apoptoses, Inflammatory,Apoptosis, Inflammatory,Caspase 1 Dependent Cell Death,Cell Death, Pyroptotic,Cell Deaths, Pyroptotic,Death, Pyroptotic Cell,Deaths, Pyroptotic Cell,Inflammatory Apoptoses,Pyroptoses,Pyroptotic Cell Deaths
D000071199 NLR Family, Pyrin Domain-Containing 3 Protein An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME. Cold Autoinflammatory Syndrome 1 Protein,NACHT, LRR and PYD Domains-Containing Protein 3,NLRP3 Protein,NACHT, LRR and PYD Domains Containing Protein 3,NLR Family, Pyrin Domain Containing 3 Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015427 Reperfusion Injury Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA. Ischemia-Reperfusion Injury,Injury, Ischemia-Reperfusion,Injury, Reperfusion,Reperfusion Damage,Damage, Reperfusion,Injury, Ischemia Reperfusion,Ischemia Reperfusion Injury,Ischemia-Reperfusion Injuries,Reperfusion Damages,Reperfusion Injuries
D016688 Mice, Inbred NOD A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked. Non-Obese Diabetic Mice,Mice, NOD,Mouse, Inbred NOD,Mouse, NOD,Non-Obese Diabetic Mouse,Nonobese Diabetic Mice,Nonobese Diabetic Mouse,Diabetic Mice, Non-Obese,Diabetic Mice, Nonobese,Diabetic Mouse, Non-Obese,Diabetic Mouse, Nonobese,Inbred NOD Mice,Inbred NOD Mouse,Mice, Non-Obese Diabetic,Mice, Nonobese Diabetic,Mouse, Non-Obese Diabetic,Mouse, Nonobese Diabetic,NOD Mice,NOD Mice, Inbred,NOD Mouse,NOD Mouse, Inbred,Non Obese Diabetic Mice,Non Obese Diabetic Mouse
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D020170 Caspase 1 A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE. ICE Protease,IL-1 beta-Converting Enzyme,Interleukin-1beta Converting Enzyme,CASP1 Caspase,IL-1 beta Convertase,IL1BC Enzyme,Interleukin-1 Converting Enzyme,Pro-Caspase-1,Procaspase-1,Caspase, CASP1,Convertase, IL-1 beta,Converting Enzyme, Interleukin-1,Converting Enzyme, Interleukin-1beta,IL 1 beta Convertase,IL 1 beta Converting Enzyme,Interleukin 1 Converting Enzyme,Interleukin 1beta Converting Enzyme,Pro Caspase 1,Procaspase 1,beta Convertase, IL-1,beta-Converting Enzyme, IL-1

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