Protective effect of epigallocatechin-3-gallate (EGCG) via Nrf2 pathway against oxalate-induced epithelial mesenchymal transition (EMT) of renal tubular cells
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This study evaluated effect of oxalate on epithelial mesenchymal transition (EMT) and potential anti-fibrotic property of epigallocatechin-3-gallate (EGCG). MDCK renal tubular cells were incubated with 0.5 mM sodium oxalate for 24-h with/without 1-h pretreatment with 25 μM EGCG. Microscopic examination, immunoblotting and immunofluorescence staining revealed that oxalate-treated cells gained mesenchymal phenotypes by fibroblast-like morphological change and increasing expression of vimentin and fibronectin, while levels of epithelial markers (E-cadherin, occludin, cytokeratin and ZO-1) were decreased. EGCG pretreatment could prevent all these changes and molecular mechanisms underlying the prevention by EGCG were most likely due to reduced production of intracellular ROS through activation of Nrf2 signaling and increased catalase anti-oxidant enzyme. Knockdown of Nrf2 by small interfering RNA (siRNA) abrogated all the effects of EGCG, confirming that the EGCG protection against oxalate-induced EMT was mediated via Nrf2. Taken together, our data indicate that oxalate turned on EMT of renal tubular cells that could be prevented by EGCG via Nrf2 pathway. These findings also shed light onto development of novel therapeutics or preventive strategies of renal fibrosis in the future.
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Antioxidants can regulate gene expression by inducing translocation of Nrf-2 from the cytosol to the nucleus, binding ARE, and inducing transcription of stress response genes GST, HO-1, and NQO1.
“In addition, antioxidants can regulate gene expression inducing the translocation of the nuclear factor-erythroid 2-related factor 2 (Nrf-2) from the cytosol to the nucleus, upon dissociation from its inhibitor, Kelch-like erythroid cell-derived protein 1 (Keap-1).”
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- Authors
- Kanlaya, R., Khamchun, S., Kapincharanon, C., & Thongboonkerd, V.
- Affiliations
- Siriraj Hospital (TH)
- Corresponding author
- Thongboonkerd, Visith
- Venue
- Scientific Reports
- Published
- 2016-07-25
- Volume
- 6
- Issue
- 1
- Pages
- 30233-30233
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4958994
- OpenAlex
- W2498518138
- Cited by
- 110
- References
- 46
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 8 · 2023: 11 · 2022: 12 · 2021: 9 · 2020: 11 · 2019: 16 · 2018: 16 · 2017: 10 · 2016: 2
- FWCI
- 13.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Mahidol University (RTA5680004)
- Office of the Higher Education Commission
- Faculty of Medicine Siriraj Hospital, Mahidol University
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Tea Polyphenols and Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- epigallocatechin gallate, Nrf2 signaling, epithelial-mesenchymal transition, oxalate, renal tubular epithelial cells, renal fibrosis, oxidative stress, catalase, vimentin, E-cadherin, MDCK cells, antifibrotic therapy
- MeSH terms
- Animals, Catechin, Dogs, Fibrosis, Humans, Kidney Tubules, Oxalates, Signal Transduction, RNA, Small Interfering, NF-E2-Related Factor 2, Epithelial-Mesenchymal Transition, Madin Darby Canine Kidney Cells
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