Apelin promotes diabetic nephropathy by inducing podocyte dysfunction via inhibiting proteasome activities

Journal of Cellular and Molecular Medicine

Caixia Guo²  Yu Liu²  Wenjie Zhao²  Shengnan Wei²  Xiaoli Zhang²  Wenying Wang¹ 

[1] Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China;Department of Pathophysiology and Pathology, Capital Medical University, Beijing, China

关键词: diabetic nephropathy;    podocyte;    proteasome;    ER stress;    apelin;    APLNR;   

DOI  :  10.1111/jcmm.12619

来源: Wiley

【 摘 要 】

Abstract

Podocyte injuries are associated with progression of diabetic nephropathy (DN). Apelin, an adipocyte-derived peptide, has been reported to be a promoting factor for DN. In this study, we aim to determine whether apelin promotes progression of DN by inducing podocyte dysfunction. kk-Ay mice were used as models for DN. Apelin and its antagonist, F13A were intraperitoneally administered for 4 weeks, respectively. Renal function and foot process proteins were analysed to evaluate the effects of apelin on kk-Ay mice and podocytes. Apelin increased albuminuria and decreased podocyte foot process proteins expression in kk-Ay mice, which is consistent with the results that apelin receptor (APLNR) levels increased in glomeruli of patients or mice with DN. In cultured podocytes, high glucose increased APLNR expression and apelin administration was associated with increased permeability and decreased foot process proteins levels. All these dysfunctions were associated with decreased 26S proteasome activities and increased polyubiquitinated proteins in both kk-Ay mice and cultured podocytes, as demonstrated by 26S proteasome activation with cyclic adenosine monophosphate (cAMP) or oleuropein. These effects seemed to be related to endoplasmic reticulum (ER) stress, as apelin increased C/EBP homologous protein (CHOP) and peiFα levels while cAMP or oleuropein reduced it in high glucose and apelin treated podocytes. These results suggest that apelin induces podocyte dysfunction in DN through ER stress which was induced by decreased proteasome activities in podocytes.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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