Tyrobp deficiency blocks NLRP3-mediated inflammation and pyroptosis to alleviate myocardial ischemia-reperfusion injury through regulating Syk

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2024-09-07 DOI:10.1016/j.tice.2024.102555

Jie Yu , Xiu’e Mu , Chang Guan , Yaqin Wang , Hongying Li

{"title":"Tyrobp deficiency blocks NLRP3-mediated inflammation and pyroptosis to alleviate myocardial ischemia-reperfusion injury through regulating Syk","authors":"Jie Yu , Xiu’e Mu , Chang Guan , Yaqin Wang , Hongying Li","doi":"10.1016/j.tice.2024.102555","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>The present study aims to investigate the biological function of Tyrobp in myocardial ischemia-reperfusion injury (MIRI) and to clarify its potential reaction mechanisms.</p></div><div><h3>Methods</h3><p>AC16 cells were induced by oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate the MIRI <em>in vitro</em>. The cell transfection technology was used to downregulate Tyrobp, followed by assessment of cell damage, apoptosis and cytokines production via Cell Counting Kit (CCK)-8 assay, lactate dehydrogenase (LDH) release assay, TUNEL and ELISA assays, respectively. Immunofluorescence assay was performed to assess GSDMD. Corresponding proteins were detected via western blotting, and Co-immunoprecipitation (Co-IP) assay was used to validate proteins interaction.</p></div><div><h3>Results</h3><p>Tyrobp was upregulated in OGD/R-exposed AC16 cells, and Tyrobp deficiency significantly alleviated OGD/R-caused cell viability loss, LDH release and cell apoptosis in AC16 cells. Meanwhile, Tyrobp deficiency inhibited the activation of NLRP3 inflammasome, reduced the production of cytokines and inhibited GSDMD intensity and GSDMD-N expression. Additionally, Tyrobp could interact with Syk and regulate Syk/NF-κB signaling. The rescue experiments showed that the above effects of Tyrobp deficiency on OGD/R-exposed AC16 cells were partly weakened by Syk overexpression.</p></div><div><h3>Conclusion</h3><p>Tyrobp deficiency alleviated MIRI by inhibiting NLRP3-mediated inflammation and pyroptosis through regulating Syk, providing a novel target for the treatment of MIRI.</p></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"91 ","pages":"Article 102555"},"PeriodicalIF":2.7000,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040816624002568","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose

The present study aims to investigate the biological function of Tyrobp in myocardial ischemia-reperfusion injury (MIRI) and to clarify its potential reaction mechanisms.

Methods

AC16 cells were induced by oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate the MIRI in vitro. The cell transfection technology was used to downregulate Tyrobp, followed by assessment of cell damage, apoptosis and cytokines production via Cell Counting Kit (CCK)-8 assay, lactate dehydrogenase (LDH) release assay, TUNEL and ELISA assays, respectively. Immunofluorescence assay was performed to assess GSDMD. Corresponding proteins were detected via western blotting, and Co-immunoprecipitation (Co-IP) assay was used to validate proteins interaction.

Results

Tyrobp was upregulated in OGD/R-exposed AC16 cells, and Tyrobp deficiency significantly alleviated OGD/R-caused cell viability loss, LDH release and cell apoptosis in AC16 cells. Meanwhile, Tyrobp deficiency inhibited the activation of NLRP3 inflammasome, reduced the production of cytokines and inhibited GSDMD intensity and GSDMD-N expression. Additionally, Tyrobp could interact with Syk and regulate Syk/NF-κB signaling. The rescue experiments showed that the above effects of Tyrobp deficiency on OGD/R-exposed AC16 cells were partly weakened by Syk overexpression.

Conclusion

Tyrobp deficiency alleviated MIRI by inhibiting NLRP3-mediated inflammation and pyroptosis through regulating Syk, providing a novel target for the treatment of MIRI.

查看原文本刊更多论文

Tyrobp 缺乏症可通过调节 Syk 阻止 NLRP3 介导的炎症和裂解，从而减轻心肌缺血再灌注损伤

目的本研究旨在探讨酪蛋白在心肌缺血再灌注损伤（MIRI）中的生物学功能，并阐明其潜在的反应机制。方法采用氧-葡萄糖剥夺/再氧合（OGD/R）诱导AC16细胞，模拟体外MIRI。然后分别通过细胞计数试剂盒（CCK）-8测定、乳酸脱氢酶（LDH）释放测定、TUNEL和ELISA测定评估细胞损伤、凋亡和细胞因子的产生。免疫荧光检测用于评估 GSDMD。结果Tyrobp在OGD/R暴露的AC16细胞中上调，Tyrobp缺乏可显著缓解OGD/R导致的AC16细胞活力下降、LDH释放和细胞凋亡。同时，Tyrobp的缺乏可抑制NLRP3炎性体的激活，减少细胞因子的产生，抑制GSDMD强度和GSDMD-N的表达。此外，Tyrobp还能与Syk相互作用，调控Syk/NF-κB信号转导。结论 Tyrobp 的缺乏通过调节 Syk 来抑制 NLRP3 介导的炎症和脓毒症，从而缓解了 MIRI，为治疗 MIRI 提供了一个新的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.