# MYO1C is a urinary extracellular vesicle biomarker and mediator of podocyte injury in diabetic nephropathy

## TL;DR

MYO1C is a promising urinary biomarker and contributes to kidney damage in diabetic nephropathy through p38 MAPK signaling.

## Contribution

MYO1C is identified as both a urinary biomarker and a mediator of podocyte injury in T2DN.

## Key findings

- A machine learning model using MYO1C achieved high accuracy in diagnosing T2DN.
- MYO1C knockdown reduced podocyte damage and inflammation in experimental models.
- MYO1C promotes podocyte injury via p38 MAPK signaling pathway activation.

## Abstract

Type 2 diabetic nephropathy (T2DN) is a major complication of type 2 diabetes and a leading cause of chronic kidney disease. This study aimed to explore Myosin IC (MYO1C) as both a candidate biomarker and elucidate its role as a mechanistic mediator of podocyte injury in T2DN. Using urinary extracellular vesicle RNA biomarkers identified from a training and validation cohort of 33 type 2 diabetes and 40 patients with T2DN, we developed a machine learning diagnostic model for T2DN. The model achieved an AUC of 0.877 in validation and performed well in an independent test cohort with an AUC of 0.824. MYO1C was identified as the most influential feature in the final model. Mechanistic investigations in vitro and in vivo revealed that high glucose and high-fat conditions induced podocyte injury, inflammation, and apoptosis, with increased MYO1C expression. MYO1C knockdown in vitro and in vivo reduced podocyte damage and inflammatory responses. MYO1C overexpression enhanced p38, p-CREB, and TNF-α levels, while p38 inhibition mitigated these effects. These findings support MYO1C not only as a potential urinary biomarker for T2DN but also as a key pathogenic driver that promotes podocyte injury via p38 MAPK signaling.

<strong>MYO1C as a Urinary Extracellular Vesicles Biomarker and Promotes Podocyte Injury via p38 MAPK Activation in Diabetic Nephropathy</strong>