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Upregulation of podocyte-secreted angiopoietin-like-4 in diabetic nephropathy

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Abstract

Podocyte injury plays a key role in the development of diabetic nephropathy (DN). Understanding the changes in podocyte structure and function in diabetes mellitus may lead to novel diagnostic tools and treatment strategies for DN. Albuminuria, histological alterations, and podocyte injury were detected at different time points in streptozotocin (STZ)-induced diabetic rats. Increased urinary albumin-to-creatinine ratios (ACR) and podocyte injury were significantly observed 4 weeks post-STZ injection. We determined the glomerular expression and distribution of angiopoietin-like 4 (Angptl4) by immunofluorescence and real-time PCR. Glomerular Angptl4 expression was mostly colocalized with synaptopodin, a podocyte marker, with substantial additional overlap with the glomerular basement membrane (GBM). This finding indicated that Angptl4 might be primarily secreted by podocytes and moved toward the GBM. Moreover, we observed by Western blot analysis and ELISA that the urinary Angptl4 level was gradually upregulated in both STZ-induced rats and diabetic patients with microalbuminuria and macroalbuminuria. We further found that the increased glomerular Angptl4 expression was closely related to the urinary ACR level and podocyte injury. In addition, the urinary Angptl4 expression was closely associated with albuminuria in the rats and patients with DN. This study is the first to show that podocyte-secreted Angptl4 is upregulated in DN and can be detected in urine. Angptl4 might function as a podocyte injury marker and could be a potential and novel diagnostic and therapeutic biomarker for DN.

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Acknowledgments

This study was supported by research Grants from the National Basic Research Program of China 973 Program (No. 2012CB517602), the National Natural Science Foundation of China (81370812), the Special Grade of China Postdoctoral Science Foundation (No. 201003463), Research Fund for the Doctoral Program of the Ministry of Education of China, and the Heilongjiang Postdoctoral Science Research Foundation (No. LBH-Q10028).

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Authors and Affiliations

  1. Department of Nephrology, 2nd Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China

    Jing Ma, Xiao Chen, Jian-Si Li, Lei Peng, Shi-Yao Wei, Shi-Lei Zhao, Tong Li, Dan Zhu, Yi-Xin He, Qiu-Ju Wei & Bing Li

  2. Department of Nephrology, 1st Affiliated Hospital of Harbin Medical University, Harbin, China

    Jing Ma & Qiu-Ju Wei

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  1. Jing Ma
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Electronic supplementary material

Fig. S1. The negative and positive controls for Angptl4 immunofluorescence.the DN group, kidney tissue from the DN rats on week 12 was stained with goat anti-rat Angptl4 antibody and the following secondary antibody; the 2nd antibody group, kidney tissue from the DN rats on week 12 was stained with secondary antibody only; the Normal group, kidney tissue from the normal rats was stained with goat anti-rat Angptl4 antibody and the following secondary antibody; the PHN group, kidney tissue from the PHN rats on day 7 was stained with goat anti-rat Angptl4 antibody and the following secondary antibody.

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Ma, J., Chen, X., Li, JS. et al. Upregulation of podocyte-secreted angiopoietin-like-4 in diabetic nephropathy. Endocrine 49, 373–384 (2015). https://doi.org/10.1007/s12020-014-0486-5

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