Genistein Mitigates High Glucose-induced Podocyte Injury by Modulating Autophagy via the mTOR Signal.

INTRODUCTION: High glucose (HG)-induced podocyte injury is closely associated with the dysregulation of autophagy processes. This study aimed to characterize autophagy-associated alterations in podocytes under HG conditions and to evaluate the effects of genistein treatment and changes on podocyte injury.
METHODS: Podocytes were cultured under normal glucose (NG) or HG conditions and treated with genistein or rapamycin. Proteomic analyses, immunoblotting, immunofluorescence, and ultrastructural examinations were performed to assess autophagy- and mTOR-related features. In parallel, functional assays were conducted to evaluate podocyte adhesion, migration, cytoskeletal organization, and integrin β1 distribution.
RESULTS: Exposure to HG reduced podocyte viability and was associated with increased mTOR phosphorylation, altered expression of autophagy-related markers, and impaired autophagic-lysosomal function. Proteomic analyses revealed the enrichment of DEPs in lysosome-, autophagy-, and mTOR-related pathways. These changes were accompanied by abnormal integrin β1 distribution, impaired cellular adhesion and migration, and cytoskeletal reorganization. Genistein treatment effectively attenuated these HG-induced changes, as evidenced by reduced mTOR phosphorylation and the restoration of autophagic-lysosomal function.
DISCUSSION: These findings indicate that HG-induced podocyte injury is accompanied by coordinated perturbations in mTOR signaling, autophagic marker expression, and integrin β1-mediated cellular functions. The observed protective effects of genistein suggest its potential regulatory role in modulating these interconnected pathways.
CONCLUSION: Genistein was associated with the alleviation of HG-induced podocyte injury, as well as changes in autophagy-lysosome-related markers and ultrastructural features suggestive of a partial restoration of autophagy- associated processes, potentially involving reduced mTOR phosphorylation.