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Alveolar epithelial-to-mesenchymal transition in scleroderma interstitial lung disease: Technical challenges, available evidence and therapeutic perspectives

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SAGE PUBLICATIONS LTD
DOI: 10.1177/23971983231181727

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Scleroderma-related interstitial lung disease; epithelial-to-mesenchymal transition; systemic sclerosis; transitional research

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The alveolar epithelial-to-mesenchymal transition is a process that involves the conversion of differentiated epithelial cells into mesenchymal-like cells through functional and morphological changes. This transition can indirectly contribute to lung fibrosis by stimulating surrounding cells, as well as directly increasing pulmonary fibroblasts and extracellular matrix deposition. Directly demonstrating this transition in scleroderma-related interstitial lung disease is challenging due to technical limitations and limited availability of lung tissue samples. However, pre-clinical and clinical evidence suggests that epithelial-to-mesenchymal transition may play a role in the development and progression of lung fibrosis in this disease.
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.

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