Smadja David M, Chocron Alberto F, Abreu M Marc
Department of Hematology, Assistance Publique - Hôpitaux de Paris, Georges Pompidou European Hospital, Paris, France.
Université Paris Cité, Institut National de la Santé et de la Recherche Médicale, Paris Cardiovascular Research Center, Paris, France.
TH Open. 2025 Jun 5;9:a25994925. doi: 10.1055/a-2599-4925. eCollection 2025.
Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone encoded by the gene, has emerged as a groundbreaking focus in thrombosis research. Recent findings published in "Science" have revolutionized our understanding of thrombosis, identifying HSP47 as a critical mediator in a new thrombosis target for treatment. This discovery not only unveils a novel pathway in thrombosis but also opens new avenues for therapeutic intervention. HSP47's significance extends beyond thrombosis, influencing pathological processes such as fibrosis and cancer. In fibrosis, its upregulation promotes collagen deposition, while its dysregulation in osteogenesis imperfecta (OI) Type X underscores the protein's indispensable role in collagen biosynthesis. The therapeutic challenge lies in balancing HSP47 inhibition to reduce fibrotic burden without impairing its essential physiological functions. In cancer, HSP47 plays dual roles. It supports tumor progression through collagen stabilization and metastasis facilitation while contributing to tissue repair under hyperthermia treatment combined with radiotherapy or chemotherapy. However, its overexpression can exacerbate tumor aggressiveness via mechanisms such as angiogenesis and epithelial-mesenchymal transition. This review emphasizes the pivotal discovery of HSP47's thrombogenic role and its broader implications in disease biology. These findings mark a paradigm shift in thrombosis research and underscore the potential of HSP47 as a target in diverse pathological contexts, from platelet-driven diseases to fibrotic and oncological disorders.
热休克蛋白47（HSP47）是一种由该基因编码的胶原蛋白特异性分子伴侣，已成为血栓形成研究中一个具有开创性的焦点。发表在《科学》杂志上的最新研究结果彻底改变了我们对血栓形成的理解，将HSP47确定为一种新的血栓形成治疗靶点中的关键介质。这一发现不仅揭示了血栓形成中的一条新途径，还为治疗干预开辟了新的途径。HSP47的重要性不仅限于血栓形成，还影响着诸如纤维化和癌症等病理过程。在纤维化过程中，其上调促进胶原蛋白沉积，而在X型成骨不全（OI）中其失调突出了该蛋白在胶原蛋白生物合成中不可或缺的作用。治疗挑战在于平衡HSP47的抑制作用，以减轻纤维化负担而不损害其基本生理功能。在癌症中，HSP47发挥着双重作用。它通过胶原蛋白稳定和促进转移来支持肿瘤进展，同时在热疗联合放疗或化疗的情况下有助于组织修复。然而，其过表达可通过血管生成和上皮-间质转化等机制加剧肿瘤侵袭性。本综述强调了HSP47促血栓形成作用这一关键发现及其在疾病生物学中的更广泛意义。这些发现标志着血栓形成研究的范式转变，并强调了HSP47作为从血小板驱动疾病到纤维化和肿瘤疾病等多种病理情况下的靶点的潜力。
