Acrolein plays a culprit role in the pathogenesis of diabetic nephropathy in vitro and in vivo

in European Journal of Endocrinology
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  • 1 Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • | 2 Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
  • | 3 School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • | 4 Department of Urology, Taipei Veterans General Hospital, Taoyuan Branch, Taoyuan, Taiwan
  • | 5 Department of Urology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • | 6 Division of Nephrology, Taoyuan Branch of Taipei Veterans General Hospital, Taoyuan, Taiwan
  • | 7 Department of Healthcare Information and Management, Ming Chuan University, Taoyuan, Taiwan
  • | 8 Department of Business Administration, Ming Chuan University, Taipei, Taiwan
  • | 9 Division of Nephrology, Department of Medicine, Taipei City Hospital, Zhongxing Branch, Taipei, Taiwan
  • | 10 Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • | 11 College of Science and Engineering, Fu Jen Catholic University, New Taipei City, Taiwan
  • | 12 Department of Special Education, University of Taipei, Taipei, Taiwan
  • | 13 Kim Forest Enterprise Co., Ltd., Taipei, Taiwan
  • | 14 Toxicology, Kaohsiung Medical University, Kaohsiung, Taiwan

Correspondence should be addressed to H-T Wang; Email: htwang01@nycu.edu.tw

*(Z-J Tong and C-W Kuo contributed equally to this work)

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Objective

Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a major chronic complication of diabetes and is the most frequent cause of kidney failure globally. A better understanding of the pathophysiology of DN would lead to the development of novel therapeutic options. Acrolein, an α,β-unsaturated aldehyde, is a common dietary and environmental pollutant.

Design

The role of acrolein and the potential protective action of acrolein scavengers in DN were investigated using high-fat diet/ streptozotocin-induced DN mice and in vitro DN cellular models.

Methods

Acrolein-protein conjugates (Acr-PCs) in kidney tissues were examined using immunohistochemistry. Renin–angiotensin system (RAS) and downstream signaling pathways were analyzed using quantitative RT-PCR and Western blot analyses. Acr-PCs in DN patients were analyzed using an established Acr-PC ELISA system.

Results

We found an increase in Acr-PCs in kidney cells using in vivo and in vitro DN models. Hyperglycemia activated the RAS and downstream MAPK pathways, increasing inflammatory cytokines and cellular apoptosis in two human kidney cell lines (HK2 and HEK293). A similar effect was induced by acrolein. Furthermore, acrolein scavengers such as N-acetylcysteine, hydralazine, and carnosine could ameliorate diabetes-induced kidney injury. Clinically, we also found increased Acr-PCs in serum samples or kidney tissues of DKD patients compared to normal volunteers, and the Acr-PCs were negatively correlated with kidney function.

Conclusions

These results together suggest that acrolein plays a role in the pathogenesis of DN and could be a diagnostic marker and effective therapeutic target to ameliorate the development of DN.

Supplementary Materials

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
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