20-Hydroxyecdysone Attenuates TGF-Β1-Induced Renal Cellular Fibrosis in Proximal Tubule Cells
Abstract
Unlabelled 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-β1 (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-β1/Smads transducer (including Smad2/3, 4, and 7), epithelial and mesenchymal markers (e.g. E-cadherin and α-smooth muscle actin) and Snail (transcriptional regulators for EMT).Results 20-HE reverses TGF-β1-induced increase in fibronectin (both intracellular and extracellular fibronectin). Simultaneously, 20-HE reverses TGF-β1-induced down-regulation of Smad7. In addition, 20-HE significantly attenuates TGF-β1-induced upregulation of Smad2/3 and pSmad2/3, and downregulation of E-Cadherin. Moreover, 20-HE dramatically suppresses TGF-β1-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-β1 and restoring tubule epithelial character by blocking the expression of Snail.
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In vitro studies associate ecdysterone with endothelial dysfunction prevention, osteoporosis prevention, glucose regulation, cytotoxic effects, antibacterial properties, immunomodulatory effects, and anti-inflammatory activities.
“Moreover, the effects on cell lines are associated with endothelial dysfunction prevention, osteoporosis prevention, glucose regulation, cytotoxic effects, antibacterial properties, immunomodulatory effects, and anti-inflammatory activities [52,53,54,55,56,57,58,60,61,62,63,64,65,66,67,68,69,70,71,72,73].”
From Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition (2024) · cites this paper as [56]
Within the in vitro studies of ecdysterone, no serious effects were reported.
“Within these studies, no serious effects were reported [52,53,54,55,56,57,58,60,61,62,63,64,65,66,67,68,69,70,71,72,73].”
From Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition (2024) · cites this paper as [56]
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- Authors
- Hung, T.-J., Chen, W.-M., Liu, S.-F., Liao, T.-N., Lee, T.-C., Chuang, L.-Y., Guh, J.-Y., Hung, C.-Y., Hung, Y.-J., Chen, P.-Y., Hsieh, P.-F., & Yang, Y.-L.
- Affiliations
- Chung Hwa University of Medical Technology (TW)
- Kaohsiung Medical University (TW)
- Chang Gung University (TW)
- Corresponding author
- Yang, Yu-Lin
- ORCID
- Venue
- Journal of Diabetes and its Complications
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 26
- Issue
- 6
- Pages
- 463-469
- ISSN
- 0891-6632 (ISSN-L)
- 1056-8727
- OpenAlex
- W2008986224
- Cited by
- 25
- References
- 20
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 1 · 2019: 1 · 2016: 1 · 2015: 1 · 2014: 3
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Diabetes and its Complications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- 20-hydroxyecdysone, TGF-β1, renal fibrosis, proximal tubular epithelial cells, HK-2 cells, fibronectin, Smad2/3, Smad7, E-cadherin, snails, epithelial-mesenchymal transition, post-receptor signaling
- MeSH terms
- Snail Family Transcription Factors, Cell Line, Diabetic Nephropathies, Ecdysterone, Fibronectins, Fibrosis, Humans, Hypoglycemic Agents, Kidney Tubules, Proximal, Osmolar Concentration, Phytosterols, Transcription Factors, Signal Transduction, Biomarkers, Down-Regulation, Up-Regulation, Protective Agents, Smad Proteins, Transforming Growth Factor beta1, Epithelial-Mesenchymal Transition, Molecular Targeted Therapy
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