College of Medical Laboratory, Dalian Medical University, Dalian 116044, China.
Department of Laboratory Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
Sci Total Environ. 2024 Nov 10;950:175328. doi: 10.1016/j.scitotenv.2024.175328. Epub 2024 Aug 6.
Exposure to fine particulate matter (PM) in the ambient environment augments susceptibility to respiratory ailments. Circular RNAs, a distinctive subclass of endogenous non-coding RNAs, have been acknowledged as pivotal regulators of pathological conditions. Ferroptosis, an innovative iron-dependent form of cellular demise, has emerged as a consequential participant in numerous maladies. Despite the established association between PM exposure and the exacerbation of asthma, scant investigations have probed into the implication of circRNAs and ferroptosis in PM-induced asthma. Consequently, this inquiry sought to scrutinize the potential involvement of circCDR1as and ferroptosis in PM-induced asthma. Through the formulation of a PM exposure model in asthmatic mice and an in vitro cellular model, it was discerned that PM induced ferroptosis, thereby intensifying asthma progression. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed an upregulation of circCDR1as in the PM-stimulated asthma cell model. Molecular biology assays demonstrated that diminished circCDR1as expression hindered the onset of ferroptosis in response to PM exposure. Notably, Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, manifested the ability to impede the advancement of asthma. Mechanistically, RNA pull-down and molecular biology experiments substantiated that circCDR1as selectively bound to insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), thereby modulating the occurrence of ferroptosis. CircCDR1as emerged as a potential orchestrator of asthma progression by regulating ferroptosis under PM exposure. Additionally, PM exposure elicited activation of the Wnt/β-catenin signaling pathway, subsequently influencing the expression of C-myc and Cyclin D1, ultimately exacerbating asthma development. In summation, the interaction between circCDR1as and IGF2BP2 in regulating ferroptosis was identified as a critical facet in the progression of asthma under PM exposure. This investigation underscores the pivotal roles of circCDR1as and ferroptosis in PM-induced asthma, offering a novel theoretical foundation for the therapeutic and preventive approaches to asthma.
暴露于环境中的细颗粒物（PM）会增加患呼吸道疾病的易感性。环状 RNA 作为内源性非编码 RNA 的一个独特亚类，已被认为是病理状态的关键调节因子。铁死亡，一种新型的铁依赖性细胞死亡形式，已成为许多疾病的重要参与者。尽管已经证实 PM 暴露与哮喘恶化之间存在关联，但很少有研究探讨 circRNAs 和铁死亡在 PM 诱导的哮喘中的作用。因此，本研究旨在探讨 circCDR1as 和铁死亡在 PM 诱导的哮喘中的潜在作用。通过在哮喘小鼠和体外细胞模型中构建 PM 暴露模型，发现 PM 诱导铁死亡，从而加剧哮喘进展。定量逆转录-聚合酶链反应（qRT-PCR）显示，PM 刺激的哮喘细胞模型中 circCDR1as 的表达上调。分子生物学测定表明，circCDR1as 表达减少抑制了 PM 暴露时铁死亡的发生。值得注意的是，铁死亡抑制剂 Ferrostatin-1（Fer-1）能够阻止哮喘的进展。机制上，RNA 下拉和分子生物学实验证实 circCDR1as 选择性结合胰岛素样生长因子 2 mRNA 结合蛋白 2（IGF2BP2），从而调节铁死亡的发生。circCDR1as 通过在 PM 暴露下调节铁死亡成为哮喘进展的潜在调控因子。此外，PM 暴露引发 Wnt/β-catenin 信号通路的激活，进而影响 C-myc 和 Cyclin D1 的表达，最终加剧哮喘的发展。总之，circCDR1as 和 IGF2BP2 在调节铁死亡中的相互作用被确定为 PM 暴露下哮喘进展的关键方面。这项研究强调了 circCDR1as 和铁死亡在 PM 诱导的哮喘中的关键作用，为哮喘的治疗和预防方法提供了新的理论基础。
