Beclin-1/LC3B regulation of podocyte autophagy in IgA nephropathy via PI3K/AKT signaling

BACKGROUND: Dysregulation of podocyte autophagy, triggering serious impairment of podocyte integrity, is a possible determinant of IgAN. To decipher the significant roles of Beclin-1 and LC3B in IgAN in regulating cellular autophagy, we investigated the role of PI3K/AKT signaling in regulating podocyte autophagy of IgAN. METHODS: To carry out this study, we obtained tissue samples from 80 patients with primary IgAN (IgAN group) and 20 patients with kidney stones (control group). The IgAN group was further classified according to the Haas pathological grading system. The 100 paraffin-embedded tissue samples underwent hematoxylin-eosin staining, immunofluorescence, special staining techniques, immunohistochemical analysis (AKT, FoxO1, Beclin-1, LC3B, nephrin and podocin), and transmission electron microscopy. RESULTS: The number of autophagosomes was generally lower in the IgAN group than in the control group, however, in the IgAN group, the number of autophagosomes showed an increasing trend, with higher Haas grade. Beclin-1 and LC3B expression levels were highly correlated, and they were positively correlated with Haas grading, with LC3B showing a "U-shaped" trend: initial low expression in early grades (I-II), progressive increase to peak at grade III, followed by a potential decline in advanced grades (IV-V). Meanwhile, AKT expression was markedly reduced in the early stages (grades I-II) but gradually increased in the late stages (grades III-V). The number of autophagosomes demonstrated a strong positive correlation with Beclin-1 and LC3B expression. CONCLUSION: Autophagy is a key player in the occurrence and progression of IgAN. Dysregulation of the autophagy pathway represents a core mechanism in the pathogenesis of IgAN, a finding supported by the strong positive correlation between Haas grading and the number of autophagosomes, as well as Beclin-1/LC3B expression.