Baicalin alleviates LPS-induced cytotoxicity in acute lung injury through mediating METTL14/SOX6 axis.

IF 2.7 3区医学 Q2 CRITICAL CARE MEDICINE SHOCK Pub Date : 2024-11-21 DOI:10.1097/SHK.0000000000002518

Yuexuan Chen, Yuhai Gu, Zhihan Gao

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Abstract

Background: Baicalin (C21H18O11) is a flavonoid component extracted from scutellaria baicalensis with biological activity in various types of diseases, including acute lung injury (ALI). The relevant mechanism behind baicalin in ALI needs further investigation.

Methods: ALI model in vitro was established by lipopolysaccharide (LPS) in WI-38 cells (lung fibroblast). Cell growth was determined via MTT assay and EdU assay. Apoptosis was assessed using flow cytometry, caspase 3 assay and TUNEL assay. Oxidative indicators and inflammatory cytokines were detected by commercial kits. Interaction between methyltransferase-like 14 (METTL14) and SRY-Box Transcription Factor 6 (SOX6) was studied using Methylated RNA Immunoprecipitation (MeRIP) and dual-luciferase reporter assay. RT-qPCR and western blot were applied for examining gene levels.

Results: Baicalin enhanced cell growth and reduced apoptosis, oxidative stress, inflammation after ALI was induced by LPS. Downregulation of SOX6 weakened LPS-induced cytotoxicity in WI-38 cells. Baicalin prevented from LPS-induced lung cell injury via reducing SOX6 expression. SOX6 expression was stabilized by METTL14 through its methylation modification. METTL14/SOX6 axis was related to the regulation of baicalin in LPS-treated WI-38 cells.

Conclusion: Therefore, baicalin played an important role to inhibit LPS-induced cytotoxicity in vitro via METTL14-mediated methylation of SOX6.

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黄芩苷通过介导METTL14/SOX6轴减轻lps诱导的急性肺损伤细胞毒性。

背景：黄芩苷（C21H18O11）是从黄芩中提取的黄酮类成分，对包括急性肺损伤（ALI）在内的多种疾病具有生物活性。黄芩苷治疗ALI的相关机制有待进一步研究。方法：采用脂多糖（LPS）在肺成纤维细胞（WI-38）中建立体外ALI模型。MTT法和EdU法检测细胞生长情况。采用流式细胞术、caspase - 3法和TUNEL法检测细胞凋亡。氧化指标和炎症因子检测试剂盒。采用甲基化RNA免疫沉淀（MeRIP）和双荧光素酶报告基因法研究甲基转移酶样14 （METTL14）与SRY-Box转录因子6 （SOX6）的相互作用。RT-qPCR和western blot检测基因表达水平。结果：黄芩苷促进细胞生长，减少LPS诱导的ALI后细胞凋亡、氧化应激、炎症反应。下调SOX6可减弱lps诱导的WI-38细胞毒性。黄芩苷通过降低SOX6的表达来预防lps诱导的肺细胞损伤。METTL14通过甲基化修饰稳定SOX6的表达。METTL14/SOX6轴与黄芩苷在lps处理的WI-38细胞中的调节作用有关。结论：黄芩苷通过mettl14介导的SOX6甲基化，在体外抑制lps诱导的细胞毒性中发挥重要作用。

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来源期刊

SHOCK 医学-外科

CiteScore

6.20

自引率

3.20%

发文量

199

审稿时长

1 months

期刊介绍： SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.