Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy

被引:23
作者
Kang, Jeong Suk [1 ,2 ]
Son, Seung Seob [1 ]
Lee, Ji-Hye [3 ]
Lee, Seong Woo [1 ,4 ]
Jeong, Ah Reum [1 ]
Lee, Eun Soo [5 ]
Cha, Seung-Kuy [6 ]
Chung, Choon Hee [5 ]
Lee, Eun Young [1 ,2 ,4 ]
机构
[1] Soonchunhyang Univ, Dept Internal Med, Cheonan Hosp, Cheonan, South Korea
[2] Soonchunhyang Univ, Coll Med, Inst Tissue Regenerat, Cheonan, South Korea
[3] Soonchunhyang Univ, Dept Pathol, Cheonan Hosp, Cheonan, South Korea
[4] Soonchunhyang Univ, Coll Med, BK21 Four Project, Cheonan, South Korea
[5] Yonsei Univ, Dept Internal Med, Wonju Coll Med, Wonju, South Korea
[6] Yonsei Univ, Dept Physiol, Wonju Coll Med, Wonju, South Korea
来源
PLOS ONE | 2021年 / 16卷 / 04期
基金
新加坡国家研究基金会;
关键词
ANGIOTENSIN-II; CELL; KIDNEY; INFLAMMATION; HYPERTROPHY; CONTRIBUTES; DEFICIENCY; EXPRESSION; STRESS;
D O I
10.1371/journal.pone.0250666
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The anti-aging gene, klotho, has been identified as a multi-functional humoral factor and is implicated in multiple biological processes. However, the effects of klotho on podocyte injury in diabetic nephropathy are poorly understood. Thus, the current study aims to investigate the renoprotective effects of klotho against podocyte injury in diabetic nephropathy. We examined lipid accumulation and klotho expression in the kidneys of diabetic patients and animals. We stimulated cultured mouse podocytes with palmitate to induce lipotoxicity-mediated podocyte injury with or without recombinant klotho. Klotho level was decreased in podocytes of lipid-accumulated obese diabetic kidneys and palmitate-treated mouse podocytes. Palmitate-treated podocytes showed increased apoptosis, intracellular ROS, ER stress, inflammation, and fibrosis, and these were significantly attenuated by klotho administration. Klotho treatment restored palmitate-induced downregulation of the antioxidant molecules, Nrf2, Keap1, and SOD1. Klotho inhibited the phosphorylation of FOXO3a, promoted its nuclear translocation, and then upregulated MnSOD expression. In addition, klotho administration attenuated palmitate-induced cytoskeleton changes, decreased nephrin expression, and increased TRPC6 expression, eventually improving podocyte albumin permeability. These results suggest that klotho administration prevents palmitate-induced functional and morphological podocyte injuries, and this may indicate that klotho is a potential therapeutic agent for the treatment of podocyte injury in obese diabetic nephropathy.
引用
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页数:20
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