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In-depth urinary and exosome proteome profiling analysis identifies novel biomarkers for diabetic kidney disease

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Abstract

Diabetic kidney disease (DKD) is a major microvascular complication of type 2 diabetes mellitus (T2DM). Monitoring the early diagnostic period and disease progression plays a crucial role in treating DKD. In this study, to comprehensively elucidate the molecular characteristics of urinary proteins and urinary exosome proteins in type 2 DKD, we performed large-scale urinary proteomics (n=144) and urinary exosome proteomics (n=44) analyses on T2DM patients with albuminuria in varying degrees. The dynamics analysis of the urinary and exosome proteomes in our study provides a valuable resource for discovering potential urinary biomarkers in patients with DKD. A series of potential biomarkers, such as SERPINA1 and transferrin (TF), were detected and validated to be used for DKD diagnosis or disease monitoring. The results of our study comprehensively elucidated the changes in the urinary proteome and revealed several potential biomarkers reflecting the progression of DKD, which provide a reference for DKD biomarker screening.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2020YFE0202200), the National Natural Science Foundation of China (22225702, 32071432, 32171434, 81600702), the Program of Shanghai Academic Research Leader (22XD1420900), the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China (KF-202201), the Innovative Research Team of High-Level Local Universities in Shanghai (SHSMU-ZDCX20212700), the Guangdong High-level New R&D Institute (2019B090904008), and the Guangdong High-level Innovative Research Institute (2021B0909050003).

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  1. Contributed equally to this work

Authors and Affiliations

  1. Department of Endocrinology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China

    Shichun Du & Shu Ye

  2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Linhui Zhai, Shu Ye, Le Wang & Minjia Tan

  3. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Guangdong, 528400, China

    Linhui Zhai & Minjia Tan

  4. Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Muyin Liu

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  1. Shichun Du
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  2. Linhui Zhai
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  4. Le Wang
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Correspondence to Shichun Du or Minjia Tan.

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Du, S., Zhai, L., Ye, S. et al. In-depth urinary and exosome proteome profiling analysis identifies novel biomarkers for diabetic kidney disease. Sci. China Life Sci. 66, 2587–2603 (2023). https://doi.org/10.1007/s11427-022-2348-0

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