Silicosis is an occupational fibrotic lung disease caused by inhaling large amounts of crystalline silica dust. Transforming growth factor-β1 (TGF-β1), which is secreted from macrophages, has an important role in the development of this disease. Macrophages can recognize and capture silicon dust, undergo M2 polarization, synthesize TGF-β1 precursors, and secrete them out of the cell where they are activated. Activated TGF-β1 induces cells from different sources, transforming them into myofibroblasts through autocrine and paracrine mechanisms, ultimately causing silicosis. These processes involve complex molecular events, which are not yet fully understood. This systematic summary may further elucidate the location and development of pulmonary fibrosis in the formation of silicosis. In this review, we discussed the proposed cellular and molecular mechanisms of production, secretion, activation of TGF-β1, as well as the mechanisms through which TGF-β1 induces cells from three different sources into myofibroblasts during the pathogenesis of silicosis. This study furthers the medical understanding of the pathogenesis and theoretical basis for diagnosing silicosis, thereby promoting silicosis prevention and treatment.
Alveolar macrophages play a vital role in the development of acute silicosis, but the dynamic changes of M1 and/or M2 phenotypes have not been elucidated. In this study, acute silicosis models of rat were established by a one-time dusting method, and the rats were sacrificed after 1, 3, 7, 14, and 28 days. The polarity states of macrophages were assessed by measuring the M1/M2 marker genes of alveolar macrophages and the M1/M2 marker proteins in bronchoalveolar lavage fluid. The pathological changes of lung tissues were examined with hematoxylin and Eosin and Masson’s trichrome staining. Our results showed that in the early stages, alveolar macrophages were mainly polarized into M1; with time, the polarization of M2 gradually became dominant. Microscopic sections showed significant pathological responses of inflammation and fibrosis. This work suggested that the alteration of alveolar macrophage polarization was involved in the lung pathologic responses to acute silicosis.
Several epidemiologic and toxicological studies have widely regarded that mitochondrial dysfunction is a popular molecular event in the process of silicosis from different perspectives, but the details have not been systematically summarized yet. Thus, it is necessary to investigate how silica dust leads to pulmonary fibrosis by damaging the mitochondria of macrophages. In this review, we first introduce the molecular mechanisms that silica dust induce mitochondrial morphological and functional abnormalities and then introduce the main molecular mechanisms that silica‐damaged mitochondria induce pulmonary fibrosis. Finally, we conclude that the mitochondrial abnormalities of alveolar macrophages caused by silica dust are involved deeply in the pathogenesis of silicosis through these two sequential mechanisms. Therefore, reducing the silica‐damaged mitochondria will prevent the potential occurrence and fatality of the disease in the future.
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