Excessive exosome release is the pathogenic pathway linking a lysosomal deficiency to generalized fibrosis

摘要: Lysosomal exocytosis is a ubiquitous process negatively regulated by neuraminidase 1 (NEU1), sialidase mutated in the glycoprotein storage disease sialidosis. In Neu1−/− mice, excessive lysosomal at basis of pathogenesis. Yet, tissue-specific molecular consequences this deregulated pathway are still unfolding. We now report that muscle connective tissue, fibroblasts have features myofibroblasts and proliferative, migratory, exocytose large amounts exosomes. These nanocarriers loaded with activated transforming growth factor–β wingless-related integration site (WNT)/β-catenin signaling molecules propagate fibrotic signals to other cells, maintaining tissue prolonged transitional status. Myofibroblast-derived exosomes fed normal convert them into myofibroblasts, changing recipient cells’ proliferative migratory properties. findings reveal an unexpected exosome-mediated downstream NEU1 deficiency propagates could be implicated idiopathic forms fibrosis humans.