TGR5在糖尿病肾小管上皮细胞凋亡中的作用机制及三七皂苷Ft1的作用

IF 4.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiang Xiao, Junlin Zhang, Yucheng Wu, Qing Yang, Yutong Zhou, Jia Yang, Yanlin Lang, Linli Cai, Xuegui Ju, Fang Liu
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引用次数: 0

摘要

TGR5及其激动剂具有调节糖脂代谢的作用。糖脂代谢紊乱引起的肾小管上皮细胞铁下垂参与了DKD的过程。本研究旨在探讨TGR5激活与三七皂苷Ft1 (Ft1)干预糖尿病肾tec铁凋亡的关系及其可能的分子机制。通过腺相关病毒9 (AAV9)过表达TGR5或Ft1干预db/db小鼠,观察其对肾损伤和铁垂的影响。此外,通过诱导高糖高棕榈酸(HGPA) HK2细胞模拟糖尿病TECs损伤模型,分别观察质粒转染过表达TGR5、siRNA沉默TGR5表达、Ft1干预对铁凋亡的影响及分子机制。在db/db小鼠中,TGR5过表达或Ft1干预减轻了肾损伤,表现为蛋白尿减少、肾小球基质扩张和肾小管损伤减轻。在HGPA培养的HK2中,过表达TGR5或干预Ft1均能抑制tec铁下垂,而沉默TGR5的表达进一步促进tec铁下垂。JNK信号通路在这一过程中发挥了重要作用。这些发现证实了TGR5激活或Ft1干预在糖尿病tec损伤和铁下垂中的重要作用,并暗示TGR5可能是糖尿病tec损伤和铁下垂的潜在治疗靶点,而Ft1可能是治疗DKD的有效药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mechanism of TGR5 in Ferroptosis of the Renal Tubular Epithelial Cells in Diabetes Mellitus and the Effect of Notoginsenoside Ft1

Mechanism of TGR5 in Ferroptosis of the Renal Tubular Epithelial Cells in Diabetes Mellitus and the Effect of Notoginsenoside Ft1

TGR5 and its agonists have the role of regulating glycolipid metabolism. The ferroptosis of renal tubular epithelial cells (TECs) caused by glycolipid metabolism disorders participates in the process of DKD. This study aims to explore the relationship between TGR5 activation and the intervention of notoginsenoside Ft1 (Ft1) and the ferroptosis of diabetic renal TECs, as well as the possible molecular mechanism. By using adeno-associated virus 9 (AAV9) to overexpress TGR5 or Ft1 to intervene in db/db mice, the effects on renal injury and ferroptosis are observed. In addition, by inducing HK2 cells with high glucose and palmitic acid (HGPA) to simulate the injury model of diabetic TECs, the effects and molecular mechanisms of plasmid transfection for overexpressing TGR5, siRNA silencing TGR5 expression, and Ft1 intervention on ferroptosis are respectively observed. In db/db mice, overexpression of TGR5 or Ft1 intervention alleviated kidney damage, manifested as a reduction in proteinuria, mesangial matrix expansion, and an alleviation of tubular injury. In HK2 cultured with HGPA, overexpression of TGR5 or Ft1 intervention could both inhibit ferroptosis of TECs, while silencing the expression of TGR5 further promoted ferroptosis of TECs. The JNK signaling pathway played an important role in this process. These findings confirm the significant role of TGR5 activation or Ft1 intervention in diabetic TECs injury and ferroptosis, and imply that TGR5 may be a potential therapeutic target for diabetic TECs injury and ferroptosis, while Ft1 may be a potent drug for the treatment of DKD.

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来源期刊
The FASEB Journal
The FASEB Journal 生物-生化与分子生物学
CiteScore
9.20
自引率
2.10%
发文量
6243
审稿时长
3 months
期刊介绍: The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
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