相关实验视频

Updated: Jun 15, 2025

Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury

Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury

Published on: May 21, 2018

METTL14/IGF2BP2-MEDIATED M6A 修改阶段1 加重的急性肺损伤引起的 SEPSIS 的修改

Junhua Lai¹, Shaochi Yu, Xia Li

¹Intensive Care Unit, Liuzhou Worker's Hospital, Liuzhou City, Guangxi, China.

Shock (Augusta, Ga.)

|August 28, 2024

概括

METTL14和IGF2BP2通过m6A修饰稳定了STEAP1mRNA,恶化了败血症引起的急性肺损伤 (ALI). STEAP1敲击改善了肺部损伤,这表明性ALI的治疗潜力.

科学领域:

分子生物学分子生物学
细胞生物学细胞生物学
免疫学免疫学免疫学

背景情况:

败血症引起的急性肺损伤 (ALI) 是一种具有高死亡率的严重疾病.
精确的调节败血性ALI的分子机制仍然不完全理解.
在与败血症相关的ALI模型中,STEAP1 (STEAP家族成员1) 被上调.

研究的目的:

调查STEAP1在败血症ALI的病变发生中的作用.
为了阐明涉及STEAP1,METTL14和IGF2BP2在败血症ALI中的调节机制.
探索针对 STEAP1 途径的潜在治疗策略.

主要方法:

在体外模型中,使用脂聚糖 (LPS) 刺激的人类肺微血管内皮细胞 (HPMEC).
基因和蛋白质表达的分析 (RT-qPCR,西式涂抹,免疫组织化学).
检测细胞活力,细胞亡,铁亡,炎症 (ELISA) 和血管生成.
研究了m6A修饰,RNA稳定性 (Actinomycin D测试) 和蛋白质-RNA相互作用 (RIP测试).
在体内验证使用多微生物败血症的老鼠模型.

主要成果:

在败血症诱导的ALI患者和用LPS治疗的HPMEC患者中,STEAP1和METTL14表达升高.
在HPMECs中,STEAP1衰竭减少了亡,炎症和铁亡,改善了管形成.
METTL14和IGF2BP2通过m6A修饰稳定了STEAP1mRNA,加剧了LPS诱导的细胞损伤.
在体内抑制METTL14或STEAP1减弱的败血症引起的肺损伤.

结论:

通过METTL14/IGF2BP2介导的STEAP1的m6A修饰在加重败血症诱导的ALI中起着至关重要的作用.
STEAP1是感染性ALI发展的关键媒介.
针对METTL14/IGF2BP2/STEAP1轴提供了一个有前途的治疗途径,用于败血性ALI.

更多相关视频

Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation

Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation

Published on: July 6, 2019

Pseudomonas aeruginosa Induced Lung Injury Model

Pseudomonas aeruginosa Induced Lung Injury Model

Published on: October 29, 2014

相关概念视频

PI3K/mTOR/AKT Signaling Pathway

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...

Regulation of the Unfolded Protein Response

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....