Chai Hongyu, Yao Shun, Gao Ya, Hu Qian, Su Wei
Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.
Int J Mol Med. 2025 Jul;56(1). doi: 10.3892/ijmm.2025.5543. Epub 2025 May 9.
Endoplasmic reticulum stress (ERS) and epithelial‑mesenchymal transition (EMT) have important roles in fibrosis and tumour development. Moderate ERS activates cellular defence mechanisms in response to noxious stimuli; however, sustained or overly strong ERS induces apoptosis. In this disease process, EMT induces epithelial cells to acquire the ability to migrate and invade. Reportedly, ERS directly or indirectly regulates EMT processes through multiple mechanisms (such as key transcription factors, signalling pathways, ferroptosis, autophagy and oxidative stress), and both processes form a complex network of interactions. Given the critical roles of ERS and EMT in disease, targeted intervention of these two processes has emerged as a potential therapeutic strategy. In the present study, the molecular interaction mechanism of ERS and EMT was systematically explored, research progress in fibrotic and neoplastic diseases was reviewed and the potential application prospects of related targeted therapies were examined, which may provide new ideas for the development of drugs to reverse fibrosis and treat tumours.
内质网应激（ERS）和上皮-间质转化（EMT）在纤维化和肿瘤发展过程中发挥着重要作用。适度的内质网应激会激活细胞防御机制以应对有害刺激；然而，持续或过度强烈的内质网应激会诱导细胞凋亡。在这个疾病过程中，上皮-间质转化促使上皮细胞获得迁移和侵袭能力。据报道，内质网应激通过多种机制（如关键转录因子、信号通路、铁死亡、自噬和氧化应激）直接或间接调节上皮-间质转化过程，并且这两个过程形成了一个复杂的相互作用网络。鉴于内质网应激和上皮-间质转化在疾病中的关键作用，针对这两个过程的干预已成为一种潜在的治疗策略。在本研究中，系统地探讨了内质网应激与上皮-间质转化的分子相互作用机制，综述了纤维化和肿瘤性疾病的研究进展，并考察了相关靶向治疗的潜在应用前景，这可能为开发逆转纤维化和治疗肿瘤的药物提供新思路。
