姜黄素在糖尿病肾病治疗中靶向 CXCL16 介导的荚膜细胞损伤和脂质蓄积。

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL
Ying Chen, Jun Tao, Yijun He, Xudong Hou, Ji Fang, Jiebo Huang, Li Wang, Junlong Shen, Bingbing Zhu, Niansong Wang, Aili Cao
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引用次数: 0

摘要

在糖尿病并发症中,糖尿病肾病(DKD)经常出现,其典型特征是通过炎症、脂质代谢失调和对荚膜细胞的伤害对肾功能产生有害影响。现有研究强调了可溶性形式的 C-X-C 趋化因子配体 16(CXCL16)在肾功能损害中的重要性。然而,CXCL16 是否参与了 DKD 的发病机制仍是一个未知数。我们报告说,DKD 患者血清和肾脏中的 CXCL16 水平升高,并与各种血脂参数相关。我们研究了高糖或棕榈酸诱导的人荚膜细胞中 CXCL16 的表达情况,以及这些细胞中外源性 CXCL16 的表达情况。CXCL16水平升高与脂质代谢异常有关。外源性 CXCL16 会诱导脂滴、微丝紊乱、细胞凋亡、氧化应激和炎症,抑制 PPAR γ,上调 COX2 的表达,并抑制 Nrf2 在荚膜细胞中的转位。分子分析表明,姜黄素(Cur)是一种从姜黄中提取的多酚化合物,也是一种 Nrf2 激动剂,可靶向 CXCL16 的 ATP 结合袋,抑制其激酶活性。同时,莪术疗法减轻了荚膜细胞损伤、脂质堆积,改善了肾小球病变,降低了白蛋白尿。此外,使用 siRNA 沉默荚膜细胞中 CXCL16 的表达后,外源性 CXCL16 的作用被抵消,Cur 也不再有任何显著影响。因此,CXCL16 参与了 DKD 的发病机制。抑制 CXCL16 在实验模型中显示出了良好的效果,这表明它对改善 DKD 有益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Curcumin targets CXCL16-mediated podocyte injury and lipid accumulation in diabetic kidney disease treatment

Among the complications of diabetes, diabetic kidney disease (DKD) frequently emerges, typified by the detrimental effects on renal function, manifesting through inflammation, dysregulated lipid metabolism, and harm to podocytes. Existing research underscores the significance of the soluble form of C-X-C chemokine ligand 16 (CXCL16) within the context of renal impairments. However, whether CXCL16 is involved in the pathogenesis of DKD remains elusive. We report that CXCL16 levels in the serum and kidneys of individuals with DKD were elevated and correlated with various lipid parameters. The expression of CXCL16 in human podocytes subjected to high glucose or palmitic acid induction and exogenous CXCL16 administration in these cells were examined. Higher CXCL16 levels were linked to abnormal lipid metabolism. Exogenous CXCL16 administration induced lipid droplets, microfilament disorganization, apoptosis, oxidative stress, and inflammation, inhibited PPAR γ, up-regulated COX2 expression, and inhibited Nrf2 translocation in podocytes. Molecular analysis revealed that Curcumin (Cur), a polyphenolic compound derived from Curcuma longa and an Nrf2 agonist, targets the ATP-binding pocket of CXCL16, inhibiting its kinase activity. Meanwhile, Cur therapy alleviated podocyte injury, lipid accumulation, improved glomerulopathy, and reduced albuminuria. Furthermore, after silencing CXCL16 expression in podocytes using siRNA, the effects of exogenous CXCL16 were nullified, and Cur no longer exhibited any significant impact. Thus, CXCL16 participates in the pathogenesis of DKD. Inhibition of CXCL16 has shown promising results in experimental models, suggesting its beneficial effects in ameliorating DKD.

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来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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