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.