circ-Katnal1 Enhances Inflammatory Pyroptosis in Sepsis-Induced Liver Injury through the miR-31-5p/GSDMD Axis.
circ-Katnal1 Enhances Inflammatory Pyroptosis in Sepsis-Induced Liver Injury through the miR-31-5p/GSDMD Axis.
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circ-Katnal1 通过 miR-31-5p/GSDMD 轴增强脓毒症引起的肝损伤中的炎症性焦亡
DOI：
10.1155/2022/8950130
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发表时间：
2022
影响因子：
4.6
通讯作者：
Yu, Kaijiang
中科院分区：
文献类型：
--
作者：
Kang, Kai;Li, Nana;Gao, Yang;Wang, Changsong;Chen, Pengfei;Meng, Xianglin;Yang, Wei;Zhao, Mingyan;Yu, Kaijiang
脓毒症是一种全身性炎症反应，严重时可引起器官功能障碍和循环系统疾病。当炎症反应特别失调时，可能会出现严重的并发症，包括脓毒症引起的肝损伤。各种microRNA沿着环状RNA参与炎症反应;然而，它们在调节脓毒症诱导的肝损伤中的功能仍然未知。盲肠结扎和穿孔（CLP）手术可诱导肝损伤以及多种微生物脓毒症。 在这项研究中，CLP被用来诱导肝损伤以及多微生物败血症。然后，肝功能，炎症细胞因子的表达，和肝脏组织病理学进行了评价。采用高通量测序技术研究CLP后肝circRNA的异常表达。采用Raw 264.7细胞模拟LPS诱导的体外脓毒症炎症模型。通过定量聚合酶链反应（PCR）和酶联免疫吸附试验探索TNF-α、IL-1β和IL-6的相对mRNA和蛋白水平。我们使用双荧光素酶报告基因检测探索了circRNA、miR-31- 5 p和gasdermin D（GSDMD）之间的功能联系。Western blot检测小鼠和细胞模型中GSDMD、caspase-1和NLRP 3的表达。 我们的研究结果表明，CLP诱导的脓毒症通过增加炎性细胞凋亡促进肝损伤。circ-Katnal 1的异常表达在CLP诱导的脓毒症中起重要作用。下调circ-Katnal 1抑制Raw 264.7细胞中LPS诱导的炎性细胞凋亡生物信息学和荧光素酶报告基因结果证实miR-31- 5 p和GSDMD是circ-Katnal 1的下游靶点。抑制miR-31- 5 p或上调GSDMD逆转了沉默circ-Katnal 1的保护作用。 综上所述，circ-Katnal 1通过miR-31- 5 p/GSDMD轴增强脓毒症诱导的肝损伤中的炎性焦亡。
Sepsis is a systemic inflammatory response that can elicit organ dysfunction as well as circulatory diseases in serious cases. When inflammatory responses are especially dysregulated, severe complications can arise, including sepsis-induced liver injury. Various microRNAs along with circular (circ) RNAs are involved in inflammatory responses; nevertheless, their functions in regulating sepsis-induced liver injury remain unknown. The cecal ligation and puncture (CLP) procedure can induce liver injury as well as polymicrobial sepsis. In this study, CLP was used to induce liver injury as well as polymicrobial sepsis. Then, liver function, inflammatory cytokine expression, and hepatic histopathology were evaluated. High-throughput sequencing was employed to investigate the abnormal hepatic circRNA expression after CLP. Raw264.7 cells were utilized to simulation an in vitro sepsis inflammation model with LPS induce. The relative mRNA as well as protein levels of TNF-α, IL-1β, and IL-6 was explored by quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays. We explored functional connections among circRNAs, miR-31-5p, and gasdermin D (GSDMD) using dual-luciferase reporter assays. Western blot was employed to test GSDMD, caspase-1, and NLRP3 expression in mice and cell models. Our results showed that CLP-induced sepsis promoted liver injury via increasing inflammatory pyroptosis. The abnormal expression of circ-Katnal1 played an important role in CLP-induced sepsis. Downregulating circ-Katnal1 suppressed LPS-induced inflammatory pyroptosis in Raw264.7 cells. Bioinformatics and luciferase reporter results confirmed that miR-31-5p and GSDMD were downstream targets of circ-Katnal1. Inhibiting miR-31-5p or upregulating GSDMD reversed the protective effects of silencing circ-Katnal1. Taken together, circ-Katnal1 enhanced inflammatory pyroptosis in sepsis-induced liver injury through the miR-31-5p/GSDMD axis.
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影响因子：
14
作者：
Selvaraj V;Nepal N;Rogers S;Manne ND;Arvapalli R;Rice KM;Asano S;Fankhanel E;Ma JJ;Shokuhfar T;Maheshwari M;Blough ER
通讯作者：
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影响因子：
64.8
作者：
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影响因子：
4.1
作者：
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通讯作者：
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影响因子：
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作者：
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