De Lorenzis Enrico, Wasson Christopher William, Del Galdo Francesco
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Division of Rheumatology, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
J Scleroderma Relat Disord. 2024 Feb;9(1):7-15. doi: 10.1177/23971983231181727. Epub 2023 Jun 20.
The alveolar epithelial-to-mesenchymal transition is the process of transformation of differentiated epithelial cells into mesenchymal-like cells through functional and morphological changes. A partial epithelial-to-mesenchymal transition process can indirectly contribute to lung fibrosis through a paracrine stimulation of the surrounding cells, while a finalized process could also directly enhance the pool of pulmonary fibroblasts and the extracellular matrix deposition. The direct demonstration of alveolar epithelial-to-mesenchymal transition in scleroderma-related interstitial lung disease is challenging due to technical pitfalls and the limited availability of lung tissue samples. Similarly, any inference on epithelial-to-mesenchymal transition occurrence driven from preclinical models should consider the limitations of cell cultures and animal models. Notwithstanding, while the occurrence or the relevance of this phenomenon in scleroderma-related interstitial lung disease have not been directly and conclusively demonstrated until now, pre-clinical and clinical evidence supports the potential role of epithelial-to-mesenchymal transition in the development and progression of lung fibrosis. Evidence consolidation on scleroderma-related interstitial lung disease epithelial-to-mesenchymal transition would pave the way for new therapeutic opportunities to prevent, slow or even reverse lung fibrosis, drawing lessons from current research lines in neoplastic epithelial-to-mesenchymal transition.
肺泡上皮-间充质转化是分化的上皮细胞通过功能和形态变化转变为间充质样细胞的过程。部分上皮-间充质转化过程可通过旁分泌刺激周围细胞间接促成肺纤维化，而完全的转化过程也可直接增加肺成纤维细胞数量并促进细胞外基质沉积。由于技术难题和肺组织样本获取有限，在硬皮病相关间质性肺疾病中直接证明肺泡上皮-间充质转化具有挑战性。同样，从临床前模型推断上皮-间充质转化的发生情况时，应考虑细胞培养和动物模型的局限性。尽管如此，虽然迄今为止该现象在硬皮病相关间质性肺疾病中的发生情况或相关性尚未得到直接和确凿的证明，但临床前和临床证据支持上皮-间充质转化在肺纤维化发生和发展中的潜在作用。整合有关硬皮病相关间质性肺疾病上皮-间充质转化的证据，将为预防、延缓甚至逆转肺纤维化的新治疗机会铺平道路，这可借鉴目前肿瘤上皮-间充质转化研究方向的经验。
