# Mesangial Cells (MES-SV40) Cultured in High Glucose Produce IL-36α, Which Is Associated with Type 2 Diabetes Mellitus

## TL;DR

High glucose conditions cause mesangial cells to produce IL-36α, which may contribute to diabetic nephropathy in type 2 diabetes.

## Contribution

This study identifies IL-36α production by mesangial cells in high glucose as a potential mechanism for diabetic nephropathy.

## Key findings

- MES-SV40 cells cultured in high glucose produce IL-36α in a dose-dependent manner.
- IL-36α promotes angiogenesis in endothelial cells, potentially initiating diabetic nephropathy.
- IL-36R expression in endothelial cells supports the role of IL-36α in this process.

## Abstract

The high concentration of the inflammatory cytokine IL-36 in the serum of patients with type 2 diabetes mellitus (T2DM), along with the reduced renal damage observed in IL-36R knockout mice following ischemia–reperfusion-induced acute kidney injury, suggests a significant association between IL-36 activity and diabetic complications such as diabetic nephropathy (DN). It is also known that minor structural alterations in glomerular tissues can lead to changes in blood vessel pressure, potentially contributing to the development of DN, with inflammation acting as a triggering factor. However, further studies are needed to confirm this relationship. In this study, we observed that mesangial (MES-SV40) cells cultured under high-glucose conditions produced IL-36α in a dose-dependent manner. This cytokine production was also detected in mesangial cells from the glomerular tissues of mice with a high-calorie diet-induced T2DM, whereas healthy mice did not show such expression. In addition, we observed that mouse endothelial cells (SVECs) showed increased tubule formation in co-culture with MES-SV40 cells that had been previously exposed to 30 mmol/L glucose, as well as with the supernatant from these cells. IL-36R expression was confirmed in endothelial cells, as well as the angiogenic effect of IL-36α. Given that elevated VEGF levels have been reported in patients with DN by other authors, our results suggest that IL-36 produced by mesangial cells under high-glucose conditions may promote angiogenesis in glomerular tissues, potentially initiating the development of diabetic nephropathy.