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ResearchIn-Press PreviewInflammationNephrology Open Access | 10.1172/jci.insight.194604

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

Zihao Zhao,1 Qianqian Yan,2 Sijie Zhou,3 Fengxun Liu,3 Yong Liu,3 Jingjing Ren,3 Shaokang Pan,3 Zhenjie Liu,3 Dongwei Liu,3 Zhangsuo Liu,3 and Jiayu Duan3

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Zhao, Z. in: PubMed | Google Scholar

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Yan, Q. in: PubMed | Google Scholar

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Zhou, S. in: PubMed | Google Scholar

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Liu, F. in: PubMed | Google Scholar

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Liu, Y. in: PubMed | Google Scholar

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Ren, J. in: PubMed | Google Scholar

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Pan, S. in: PubMed | Google Scholar

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Liu, Z. in: PubMed | Google Scholar

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Liu, D. in: PubMed | Google Scholar

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Liu, Z. in: PubMed | Google Scholar

1Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

2Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China

3Nephrology Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Find articles by Duan, J. in: PubMed | Google Scholar

Published January 22, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.194604.
Copyright © 2026, Zhao et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 22, 2026 - Version history
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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 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 T2DN patients, 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, thereby highlighting its therapeutic promise.

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