High Dose Vitamin E Attenuates Diabetic Nephropathy via Alleviation of Autophagic Stress

作者：Yuxue Zhao, Wenting Zhang, Qi Jia, Zhendong Feng, Jing Guo, Xueting Han, Yuning Liu, Hongcai Shang, Yaoxian Wang, Wei Jing Liu · 发表于：Frontiers in Physiology · 年份：2019 · DOI：10.3389/fphys.2018.01939 · 被引用次数：54 · 研究领域：Autophagy in Disease and Therapy、Advanced Glycation End Products research、Retinal Diseases and Treatments

It has been reported that autophagic stress, which is involved in many diseases, plays a key role in the development of diabetic nephropathy (DN). In this study, we investigated the effects of high dose vitamin E on renal tubular epithelial cells and autophagic stress-related mechanisms in diabetes condition. In diabetic rats, high dose vitamin E treatment significantly decreased the serum creatinine, urea nitrogen, urinary albumin and urinary protein, reduced the levels of LCN2, HAVCR1, LDH and 8-OHdG in urine, and attenuated the cellular apoptosis and interstitial fibrosis in renal cortex. In vitro, vitamin E could reduce the release of LCN2 and HAVCR1 and the protein levels of caspase 3 and TGF-β1, as well as improve the growth inhibition in cultured HK-2 cells after exposure to advanced glycation end products (AGEs). Also, LC3-II and SQSTM1-positive dots were significantly increased in the renal tubular epithelial cells of DN patients and diabetic rats, and in HK-2 cells after exposure to AGEs, which were markedly declined by vitamin E. In addition, we found that the autophagosome formation was not affected by AGEs, as assessed by the mRNA levels of LC3B, Beclin-1, and ATG7. However, AGEs blocked the lysosomal degradation of autophagosome, which was characterized by a decrease in the enzymatic activity of cathepsin B/cathepsin L and DQ-ovalbumin degradation in HK-2 cells, indicating that AGEs-induced accumulation of autophagic vacuoles was a sign of autophagic stress. Int...