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Extracellular Vesicles Facilitate the Crosstalk Between High Glucose-Stimulated Mesangial Cells and Healthy Podocytes to Mediate Injury Responses

Year: 2026

Type: article

Abstract: Mesangial cells (MCs) communicate with podocytes and contribute to podocyte damage in diabetes. We hypothesized that intercellular communication plays a critical role in glomerular injury in diabetic nephropathy (DN). This study investigated the role of extracellular vesicles (EVs) secreted by high glucose-treated MCs in podocyte dysfunction. MCs were cultured with normal or high glucose for 24 h, and control EVs (C-EVs) and high-glucose EVs (HG-EVs) were isolated and incubated with healthy podocytes. Immunofluorescence, qRT-PCR, and Western blotting assessed podocyte and profibrotic marker expression. High glucose increased the overall amount of EVs released by MCs, but not their size. HG-EVs induced upregulation of epithelial-mesenchymal transition (EMT) markers, including desmin and TGF-β1, and downregulation of podocyte markers alpha-actinin-4, synaptopodin, and P-cadherin. In a co-culture of high-glucose MCs and podocytes, an exosome secretion inhibitor attenuated these injurious effects. These data suggest that HG-EVs impair podocyte function and mediate communication between MCs and podocytes. Mesangial cell-derived EVs may represent potential therapeutic targets in DN.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27041927

Authors: Antonio S. Novaes, Raphael J. F. Felizardo, Niels O. S. Camara, Shipra Agrawal, Mirian A. Boim

Institutions: Stony Brook University, Universidade Federal de São Paulo, Universidade de São Paulo

Language: English

Topic: Extracellular vesicles in disease

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499