The multifaceted role of macrophage mitophagy in SiO2-induced pulmonary fibrosis: A brief review.

Prolonged exposure to environments with high concentrations of crystalline silica (CS) can lead to silicosis. Macrophages play a crucial role in the pathogenesis of silicosis. In the process of silicosis, silica (SiO2) invades alveolar macrophages (AMs) and induces mitophagy which usually exists in three states: normal, excessive, and/or deficiency. Different mitophagy states lead to corresponding toxic responses, including successful macrophage repair, injury, necrosis, apoptosis, and even pulmonary fibrosis. This is a complex process accompanied by various cytokines. Unfortunately, the details have not been fully systematically summarized. Therefore, it is necessary to elucidate the role of macrophage mitophagy in SiO2-induced pulmonary fibrosis by systematic analysis on the literature reports. In this review, we first summarized the current data on the macrophage mitophagy in the development of SiO2-induced pulmonary fibrosis. Then, we introduce the molecular mechanism on how SiO2-induced mitophagy causes pulmonary fibrosis. Finally, we focus on introducing new therapies based on newly developed mitophagy-inducing strategies. We conclude that macrophage mitophagy plays a multifaceted role in the progression of SiO2-induced pulmonary fibrosis, and reprogramming the macrophage mitophagy state accordingly may be a potential means of preventing and treating pulmonary fibrosis.

The role of mitochondrial dysfunction in macrophages on SiO2 -induced pulmonary fibrosis: A review.

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.