Effect of echinacoside on kidney fibrosis by inhibition of TGF-β1/Smads signaling pathway in the db/db mice model of diabetic nephropathy.

Effect of echinacoside on kidney fibrosis by inhibition of TGF-β1/Smads signaling pathway in the db/db mice model of diabetic nephropathy.
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DOI:
10.2147/dddt.s143805
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发表时间:
2017
期刊:
Drug design, development and therapy
影响因子:
--
通讯作者:
Qin J
Qin J
中科院分区:
其他
文献类型:
--
作者:
Tang F;Hao Y;Zhang X;Qin J

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肾脏纤维化和肾小管上皮间质转化(EMT)是糖尿病肾病(DN)的主要病理改变,最终导致终末期肾病。先前的研究表明松果菊苷 (ECH) 具有抗肝脏纤维化作用。然而,ECH对DN肾纤维化的影响及其机制尚不清楚。本研究旨在探讨ECH对DN db/db小鼠模型肾纤维化的影响以及ECH的分子机制。我们的结果表明,相对于 db/db 小鼠,ECH 组小鼠的一般状态有所改善,血糖和 24 小时尿蛋白水平降低。由于ECH治疗,肾功能恶化被延迟。我们还观察到ECH可以改善db/db小鼠肾脏的组织病理学结果,包括胶原沉积、系膜细胞和系膜基质增生、基底膜增厚和足细胞减少。此外,在 DN db/db 小鼠模型中,ECH 抑制 TGF-β1/Smads 信号通路,下调纤连蛋白 (FN)、IV 型胶原蛋白和 α-平滑肌肌动蛋白 (α-SMA) 水平,并上调 E-钙粘蛋白水平。我们的研究结果表明,ECH 对 DN 具有治疗作用,包括抑制肾小管 EMT 和肾纤维化。此外,ECH 通过调节 TGF-β1/Smads 信号通路抑制肾纤维化。
Kidney fibrosis and renal tubular epithelial-to-mesenchymal transition (EMT) are the main pathological changes of diabetic nephropathy (DN), which eventually leads to end-stage renal disease. Previous studies have suggested that echinacoside (ECH) is antifibrotic in the liver. However, the effect of ECH on kidney fibrosis in DN and its mechanisms are unknown. This study was performed to explore the effect of ECH on kidney fibrosis and also the molecular mechanisms of ECH in a db/db mice model of DN. Our results showed that, relative to db/db mice, the mice in the ECH group had an improved general state and reduced blood glucose and 24-hour urinary protein levels. The deterioration of renal function was delayed due to treatment with ECH. We also observed that ECH can improve histopathological findings in the kidneys of db/db mice, including collagen deposition, mesangial cell and mesangial matrix hyperplasia, basement membrane thickening, and podocyte reduction. Moreover, ECH inhibited the TGF-β1/Smads signaling pathway, downregulated fibronectin (FN), collagen IV, and alpha-smooth muscle actin (α-SMA) levels, and upregulated E-cadherin level in the db/db mice model of DN. Our findings indicate that ECH has a therapeutic effect on DN, including the inhibition of renal tubular EMT and kidney fibrosis. Furthermore, ECH inhibits kidney fibrosis through regulation of the TGF-β1/Smads signaling pathway.
DOI: 10.4103/2230-8210.119506
发表时间: 2013-10
影响因子: --
作者:
Agarwal P
通讯作者: Agarwal P