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纤维化疾病:从信号通路、生物标志物到分子成像

Fibrotic Disease: from Signaling Pathways and Biomarkers to Molecular Imaging.

作者信息

Ghazaiean Mobin, Riss Patrick J, Mardanshahi Alireza, Molavipordanjani Sajjad

机构信息

Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Gut and Liver Research Center, Non-Communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Mol Imaging Biol. 2025 Aug 11. doi: 10.1007/s11307-025-02038-9.

Abstract

Fibrotic diseases are characterized by excessive accumulation of extracellular matrix (ECM) components following tissue injury, ultimately leading to organ dysfunction and failure. The progression of fibrosis is governed by complex molecular signaling pathways, including TGF-β, PDGF, FGF, CTGF, VEGF, and many others, which regulate myofibroblast activation, ECM production, and tissue remodeling. Traditional diagnostic modalities such as magnetic resonance imaging (MRI), computed tomography (CT), and biopsy are limited in their ability to distinguish active fibrogenesis from established fibrosis or detect early molecular changes. Recent advances in molecular imaging such as the development of targeted radiotracers and MRI contrast agents-have enabled more precise detection and characterization of fibrotic processes at both preclinical and clinical levels. The integration of molecular imaging with targeted probes holds promise for improving early diagnosis, guiding therapeutic strategies, and advancing clinical management of fibrosis. This review presents a comprehensive overview of the molecular mechanisms underlying fibrogenesis, highlights key signaling pathways and biomarkers, and discusses current and emerging molecular imaging agents for fibrotic diseases diagnosis and monitoring.

摘要

纤维化疾病的特征是组织损伤后细胞外基质(ECM)成分过度积累,最终导致器官功能障碍和衰竭。纤维化的进展受复杂分子信号通路的调控,包括转化生长因子-β(TGF-β)、血小板衍生生长因子(PDGF)、成纤维细胞生长因子(FGF)、结缔组织生长因子(CTGF)、血管内皮生长因子(VEGF)等许多因子,这些因子调节肌成纤维细胞活化、ECM产生和组织重塑。传统的诊断方法,如磁共振成像(MRI)、计算机断层扫描(CT)和活检,在区分活跃的纤维化形成与已形成的纤维化或检测早期分子变化方面能力有限。分子成像领域的最新进展,如靶向放射性示踪剂和MRI造影剂的开发,使得在临床前和临床水平上对纤维化过程进行更精确的检测和表征成为可能。分子成像与靶向探针的结合有望改善纤维化的早期诊断、指导治疗策略并推进临床管理。本综述全面概述了纤维化形成的分子机制,强调了关键信号通路和生物标志物,并讨论了用于纤维化疾病诊断和监测的现有及新兴分子成像剂。

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