Babu Santha Aswani, Mangala Hegde, Ravichandran Vishwa, Mohammed S Alqahtani, Mohamed Abbas, Hassan Ali Almubarak, Gautam Sethi, Ajaikumar B Kunnumakkara
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引用次数: 0
摘要
核受体(NRs)是协调人体发育、宿主防御和体内平衡等重要功能的关键转录因子。NRs 因其作为治疗靶点的潜力而受到越来越多的关注,针对 NRs 的药物在阻碍慢性疾病进展方面具有显著疗效。因此,这些药理制剂有望治疗和控制各种疾病。不断积累的证据强调了外泌体衍生的微小核糖核酸(miRNA)在慢性炎症、疾病进展和耐药性中的调控作用,主要是通过调节转录因子,特别是 NRs。通过利用蛋白激酶 B(Akt)/哺乳动物雷帕霉素靶标(mTOR)、核因子卡巴-B(NF-κB)、转录信号转导和激活因子 3(STAT3)以及 Wnt/β-catenin 信号转导等炎症通路,外泌体和 NRs 在发育、生理和病理全景中发挥着关键作用。外泌体的内化会调节 NRs 并启动多种自分泌或旁分泌信号级联,影响受体细胞的各种过程,如存活、增殖、分化、新陈代谢和细胞防御机制。这篇综合性综述细致研究了外泌体介导的 NR 调节参与动脉粥样硬化、癌症、糖尿病、肝病和呼吸系统疾病等慢性疾病的发病机制。此外,它还阐明了外泌体介导的宿主和受体细胞之间通过 NRs 进行交流并导致免疫调节的复杂分子机制。此外,它还概述了外泌体调控的 NR 通路在预防慢性炎症方面的意义、目前的局限性,并提供了对未来前景的见解。本综述还介绍了关于外泌体及其成分在治疗耐药性出现中的作用的现有证据。
Tackling exosome and nuclear receptor interaction: an emerging paradigm in the treatment of chronic diseases.
Nuclear receptors (NRs) function as crucial transcription factors in orchestrating essential functions within the realms of development, host defense, and homeostasis of body. NRs have garnered increased attention due to their potential as therapeutic targets, with drugs directed at NRs demonstrating significant efficacy in impeding chronic disease progression. Consequently, these pharmacological agents hold promise for the treatment and management of various diseases. Accumulating evidence emphasizes the regulatory role of exosome-derived microRNAs (miRNAs) in chronic inflammation, disease progression, and therapy resistance, primarily by modulating transcription factors, particularly NRs. By exploiting inflammatory pathways such as protein kinase B (Akt)/mammalian target of rapamycin (mTOR), nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and Wnt/β-catenin signaling, exosomes and NRs play a pivotal role in the panorama of development, physiology, and pathology. The internalization of exosomes modulates NRs and initiates diverse autocrine or paracrine signaling cascades, influencing various processes in recipient cells such as survival, proliferation, differentiation, metabolism, and cellular defense mechanisms. This comprehensive review meticulously examines the involvement of exosome-mediated NR regulation in the pathogenesis of chronic ailments, including atherosclerosis, cancer, diabetes, liver diseases, and respiratory conditions. Additionally, it elucidates the molecular intricacies of exosome-mediated communication between host and recipient cells via NRs, leading to immunomodulation. Furthermore, it outlines the implications of exosome-modulated NR pathways in the prophylaxis of chronic inflammation, delineates current limitations, and provides insights into future perspectives. This review also presents existing evidence on the role of exosomes and their components in the emergence of therapeutic resistance.
期刊介绍:
Military Medical Research is an open-access, peer-reviewed journal that aims to share the most up-to-date evidence and innovative discoveries in a wide range of fields, including basic and clinical sciences, translational research, precision medicine, emerging interdisciplinary subjects, and advanced technologies. Our primary focus is on modern military medicine; however, we also encourage submissions from other related areas. This includes, but is not limited to, basic medical research with the potential for translation into practice, as well as clinical research that could impact medical care both in times of warfare and during peacetime military operations.