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

## TL;DR

The study shows that high glucose levels in mesangial cells lead to extracellular vesicles that harm healthy podocytes, contributing to kidney damage in diabetes.

## Contribution

The study reveals a novel mechanism of mesangial-podocyte crosstalk via extracellular vesicles in diabetic nephropathy.

## Key findings

- High glucose increases extracellular vesicle release from mesangial cells without altering their size.
- Extracellular vesicles from high glucose-treated mesangial cells induce podocyte dysfunction and EMT markers.
- Blocking exosome secretion reduces the harmful effects on podocytes in co-culture.

## 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.