20-Hydroxyecdysone attenuates TGF-β1-induced renal cellular fibrosis in proximal tubule cells

被引：24

作者：

Hung, Tsung-Jen ^{[1
]}

Chen, Wei-Ming ^{[1
]}

Liu, Shu-Fen ^{[2
]}

Liao, Tung-Nan ^{[3
]}

Lee, Tao-Chen ^{[4
]}

Chuang, Lea-Yea ^{[5
]}

Guh, Jinn-Yuh ^{[2
]}

Hung, Chien-Ya ^{[6
]}

Hung, Yu-Ju ^{[7
]}

Chen, Po-yi ^{[8
]}

Hsieh, Pei-fang ^{[1
]}

Yang, Yu-Lin ^{[1
,2
,3
]}

机构：

[1] Chung Hwa Univ Med Technol, Dept Grad Inst Biomed Sci, Tainan, Taiwan

[2] Kaohsiung Med Univ, Dept Internal Med, Kaohsiung, Taiwan

[3] Chung Hwa Univ Med Technol, Dept Med Lab Sci & Biotechol, Tainan, Taiwan

[4] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Kaohsiung, Taiwan

[5] Kaohsiung Med Univ, Dept Biochem, Kaohsiung, Taiwan

[6] Chung Hwa Univ Med Technol, Dept Food Nutr, Tainan, Taiwan

[7] Natl Taiwan Univ, Dept Publ Hlth, Taipei 10764, Taiwan

[8] Chung Hwa Univ Med Technol, Dept Optometry, Tainan, Taiwan

来源：

JOURNAL OF DIABETES AND ITS COMPLICATIONS | 2012年 / 26卷 / 06期

关键词：

TGF-beta; Epithelial-to-Mesenchymal transition (EMT); 20-hydroxyecdysterone (20-HE); GENE-EXPRESSION; TRANSITION;

D O I：

10.1016/j.jdiacomp.2012.06.014

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Renal fibrosis progresses to end stage of diabetes kidney disease, which causes irreversible progressive proximal tubular injury. In a previous study, 20-hydroxyecdysterone (20-HE), a phytoecdysteroid, attenuated renal injury in diabetes models. However, the fibrosis regulatory role remains to be investigated. Methods: The proximal tubular epithelial cells (designated as HK-2) were treated for 48 h with TGF-beta 1 (5 ng/ml) in different concentrations of 20-HE (0 to 500 nM/ml) in the last 24 h of culture. The extracellular fibronectin was measured by ELISA assay. Western blot and immunofluorescence were used to evaluate the expression of TGF-beta 1/Smads transducer (including Smad2/3, 4, and 7), epithelial and mesenchymal markers (e.g. E-cadherin and alpha-smooth muscle actin) and Snail (transcriptional regulators for EMT). Results: 20-HE reverses TGF-beta 1-induced increase in fibronectin (both intracellular and extracellular fibronectin). Simultaneously, 20-HE reverses TGF-beta 1-induced down-regulation of Smad7. In addition, 20-HE significantly attenuates TGF-beta 1-induced upregulation of Smad2/3 and pSmad2/3, and downregulation of E-Cadherin. Moreover, 20-HE dramatically suppresses TGF-beta 1-induced increases in the expression of Snail. Conclusion: We propose that 20-HE is a potential fibrosis antagonist for renal proximal tubule cells. 20-HE might act through suppressing post-receptor signaling of TGF-beta 1 and restoring tubule epithelial character by blocking the expression of Snail. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：463 / 469

页数：7