首页|miR-22-3p靶向GSDMD抑制同型半胱氨酸诱导的平滑肌细胞焦亡

miR-22-3p靶向GSDMD抑制同型半胱氨酸诱导的平滑肌细胞焦亡

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目的 探讨miR-22-3p对同型半胱氨酸(Hey)诱导血管平滑肌细胞焦亡的影响。方法 体外培养人血管平滑肌细胞(VSMC)，分为 Control 组(0 μmol/L Hey)与 Hey 组(100 μmol/L Hey)，Western blot 检测细胞中pro Caspase-1、GSDMD、N-GSDMD、NLRP3 表达水平，qRT-PCR 检测 miR-22-3p 表达情况;ELISA 检测上清中 IL-1β、IL-18 的浓度。转染 miR-22-3p 对照(miR-22-3p-NC)、miR-22-3p 的模拟物(miR-22-3p-mimic)及抑制物(miR-22-3p-inhibitor)后观察 Hey 诱导下 VSMC 的变化。结果 与 Control 组相比，Hey 组 VSMC 中 pro Caspase-1、GSDMD、N-GSDMD、NLRP3 表达水平增加(P＜0。05)，IL-1β、IL-18 浓度更高(P＜0。01)，miR-22-3p 相对表达水平低(P＜0。01);转染 miR-22-3p-mimic 后，VSMC 中 pro Caspase-1、GSDMD、N-GSDMD、NLRP3 表达水平显著降低(P＜0。01)，IL-1β、IL-18 浓度降低(P＜0。01);转染 miR-22-3p-inhibitor 后 VSMC 中 pro Caspase-1、GSDMD、N-GSDMD、NLRP3 表达水平显著增加(P＜0。01)，IL-1β、IL-18浓度升高(P＜0。05)。结论 miR-22-3p可抑制Hey诱导的VSMC焦亡。
MiR-22-3p targets gasdermin D to inhibit homocysteine-induced pyroptosis of vascular smooth muscle cells
Objective To investigate the effect of miR-22-3p on pyroptosis of vascular smooth muscle cells(VSMCs)induced by homocysteine(Hcy).Methods Human VSMCs were cultured in vitro and divided into a Control group(0 μmol/L Hey)and a Hey group(100 μmol/L Hey).After intervention,expression levels of pro Caspase-1,gasdermin D(GSDMD),N-GSDMD,and NLR family pyrin domain containing 3(NLRP3)were detected by Western blot.MiR-22-3p expression was determined by quantitative real-time reverse-transcription polymerase chain reaction.Interleukin(IL)-1 β and IL-18 levels in the supernatant were measured by enzyme-linked immunosorbent assay.Cells were also transfected with control miR-22-3p(miR-22-3p-NC),miR-22-3p-mimic,and miR-22-3p-inhibitor,to observe the effects on VSMC pyroptosis induced by Hcy.Results Expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs were increased(P＜0.05),IL-1 β and IL-18 levels were increased(P＜0.01),and the relative expression level of miR-22-3p was reduced(P＜0.01)in the Hcy group compared with the Control group.Transfection with miR-22-3p-mimic significantly decreased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P＜0.01),and significantly decreased levels of IL-1β and IL-18(P＜0.01),while transfection with miR-22-3p-inhibitor significantly increased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P＜0.01)and significantly increased the levels of IL-1β and IL-18(P＜0.05).Conclusions MiR-22-3p may delay Hcy-induced VSMC pyroptosis.

atherosclerosisVSMCpyroptosismiR-22-3phomocysteine

钟颖怡、丁宁、王浥尘、刘超、董治锋、马胜超、熊建团、郝银菊、白志刚、姜怡邓

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国家卫生健康委代谢性心血管疾病研究重点实验室,银川 750004

宁夏医科大学基础医学院,银川 750004

宁夏医科大学临床医学院,银川 750004

宁夏回族自治区人民医院,银川 750004

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动脉粥样硬化 血管平滑肌细胞 焦亡 miR-22-3p 同型半胱氨酸

国家自然科学基金项目国家自然科学基金项目国家自然科学基金项目宁夏回族自治区重点研发计划重点项目宁夏回族自治区重点研发计划重点项目宁夏回族自治区重点研发计划重点项目宁夏回族自治区重点研发计划重点项目

U21A2034382370293822704922023BEG020742022BFH020132021BEG020332020BFH02001

2024

10.3969/j.issn.1671-7856.2024.09.002

中国比较医学杂志
中国实验动物学会，中国医学科学院医学实验动物研究所

中国比较医学杂志

CSTPCD北大核心
影响因子：0.473
ISSN：1671-7856
年,卷(期)：2024.34(9)