The aggravate role of exosomal circRNA11:120406118|12040782 on macrophage pyroptosis through miR-30b-5p/NLRP3 axis in silica-induced lung fibrosis

Silica dust inhalation could lead to silicosis, and there is no specific biomarker for its early diagnosis and no effective treatment due to the lack of research on its pathogenesis. The homeostasis of macrophages was considered to be crucial during the development of silicosis from persistent chronic inflammation to irreversible fibrosis. However, its regulatory mechanism and the communication between macrophages and others are still not clear. Exosomal circRNAs emerge as favorable candidates for cellular communication. Therefore, our study aimed to illustrate the regulatory mechanism of silicosis from the view of exosomal circRNAs. Our study identified a novel exosomal circRNA, circRNA11:120406118|12040782, in the peripheral serum of silicosis patients. Furthermore, the detailed role of circRNA11:120406118|12040782 was investigated both in silicosis mouse model and in silica-stimulated macrophages and fibroblasts. On the one hand, circRNA11:120406118|12040782 was shown to regulate silica-stimulated macrophage pyroptosis through circRNA11:120406118|12040782/miR-30b-5p/NLRP3 network. And this macrophage-derived cirRNA could promote the activation of fibroblasts. On the other hand, overexpressing miR-30b-5p, the crucial component of circRNA11:120406118|12040782/miR-30b-5p/NLRP3 regulatory network, could inhibit pyroptosis and attenuate silica-induced lung inflammation and fibrosis in mice. Our findings suggested that exosomal circRNA11:120406118|12040782 could aggravate NLRP3-mediated macrophages pyroptosis through sponging miR-30b-5p in silicosis development, which provide an experimental basis and shed light on the early diagnosis and treatment of silicosis.