The PM2.5 component, benzo[b]fluoranthene, may contribute to the pathogenesis of membranous nephropathy by activating phosphoinositide 3-kinase/protein kinase B pathway and causing podocyte pyroptosis

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Membranous nephropathy (MN) is the main type of adult nephrotic syndrome, and its prevalence is increasing annually. An increasing number of studies have suggested that the pathogenesis of MN is related to 2.5-μm particulate matter (PM2.5), but the underlying mechanism has not been elucidated fully. Elucidating this mechanism can help prevent and treat MN. The constituents of PM2.5 vary from place to place; hence, the component responsible for PM2.5-related MN is still unclear. This study investigated the effects of benzo[ b ]fluoranthene (BbF), a PM2.5 component, on pyroptosis and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signalling pathway in Sprague-Dawley rats and mouse podocytes. The organic constituents of BbF in PM2.5 can enter the circulatory system through the lungs and act on the kidneys to cause kidney damage, possibly because BbF activates the PI3K/AKT pathway and causes podocytes to undergo pyroptosis. Based on the above studies, we hypothesize that BbF in PM2.5 enters the body through the respiratory tract, enters the kidney through the blood circulation, reaches the podocyte activation PI3K/AKT pathway, and promotes podocyte pyroptosis, contributing to membranous nephropathy. • Elevated Levels in Patients: Benzo[ b ]fluoranthene levels are significantly elevated in patients with membranous nephropathy, suggesting a potential link to the disease's pathology. • Systemic Entry and Renal Impact: Benzo[ b ]fluoranthene enters the circulatory system via pulmonary absorption, subsequently contributing to renal injury. • Mechanism of Podocyte Damage: Benzo[ b ]fluoranthene induces pyroptosis in podocytes through the activation of the PI3K/AKT signalling pathway, highlighting a molecular mechanism underlying kidney damage. • Innovative Administration Technique: Visual tracheal instillation offers a more precise method for delivering benzo[ b ]fluoranthene into the respiratory tract compared to traditional techniques, enhancing experimental accuracy and reliability.

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