The role of macrophage-derived TGF-β1 on SiO₂-induced pulmonary fibrosis: A review

Abstract

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.

TIM-4 in macrophages contributes to nasal polyp formation through the TGF-β1–mediated epithelial to mesenchymal transition in nasal epithelial cells

“…The results suggest that TGF-b1 synthesis and secretion in macrophages partly depend on TIM-4, and MMPs may be mediated by other factors. After being secreted out of the macrophages, the TGF-b1 could bind to TGF-b1 receptors on epithelial cells and promote EMT through TGF-b1/Smad pathway (52).…”

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“…And in the lung repair process, M2 macrophages are responsible for the regulation of fibrogenesis, which aggravates the progression of pulmonary fibrosis 35,36 . M2 macrophages can secrete excess TGF-β to enhance the proliferation and differentiation of lung fibroblasts and thus facilitate the progression of pulmonary fibrosis 37 . Moreover, a previous study has revealed that PM exposure could trigger epithelial-mesenchymal transition (EMT) in alveolar epithelial cells 38 .…”

Altered M1/M2 polarization of alveolar macrophages is involved in the pathological responses of acute silicosis in rats in vivo

“…The pathogenesis of acute silicosis remains unclear. Recent studies suggested that alveolar macrophages, the first line of defense against invading lungs (Balhara and Gounni, 2012), have an important role in the development of silicosis (Zhang et al, 2019b(Zhang et al, , 2021.…”

“…The pathogenesis of acute silicosis remains unclear. Recent studies suggested that alveolar macrophages, the first line of defense against invading lungs (Balhara and Gounni, 2012), have an important role in the development of silicosis (Zhang et al, 2019b, 2021). Two hallmarks of macrophages are diversity and plasticity due to their phenotype responses to a variety of different stimuli of the tissue microenvironment (Gordon and Plűddemann, 2013; Arora et al, 2018).…”