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Bioactive Compounds of Green Teas Improve High Glucose-
induced Senescence of Renal Tubular Cells by Regulating
SIRT1/PGC-1α Axis
Rattiyaporn Kanlaya, Kanokwan Nonthawong, Chonicha Subkod, Supanan Nanthawuttiphan,
Visith Thongboonkerd*
Medical Proteomics Unit, Research Department, Faculty of Medicine, Siriraj Hospital, Mahidol University
*Corresponding Author E-mail: vthongbo@yahoo.com
Abstract
Background: Diabetic nephropathy is a severe complication arising from diabetes-induced kidney
damage, contributing to renal failure globally. Recent studies underscore the complex
relationship between DN and cellular senescence.
Methods: We evaluate the anti-senescence properties of the top three most abundant phytochemicals
in green tea, namely epigallocatechin-3-gallate, L-theanine, and theophylline, in proximal
tubular epithelial cells (PTEC) exposed to high glucose for 72 h. The conditioned medium
collected from each condition was also used to treat distal tubular cells and fibroblasts for
24 h.
Results: High glucose treatment induced various senescence markers in PTECs, e.g. cell enlargement,
increased ᵦ-galactosidase activity, increased p21 levels, S phase arrest, suppressed cellular
metabolic activity, and elevated senescence-associated secretory phenotype (SASP)
production compared to controls. Moreover, conditioned medium collected from high
glucose-treated PTEC triggered the epithelial-mesenchymal transition (EMT) of distal
tubular epithelial cells (MDCK) and activated fibroblasts (BHK-21). Accordingly, MDCK
cells undergoing EMT upregulated vimentin and fibronectin but downregulated E-cadherin
and ZO-1. Activated BHK-21 increased fibronectin, collagen 1α, vimentin, and actin
stress fiber formation. However, pre- and co-treatment with the bioactive compounds
effectively reversed these effects, potentially via SIRT/PGC-1α activation.
Conclusions: In summary, this study highlights the dual anti-senescence and anti-fibrotic properties of
these compounds in counteracting high glucose-induced senescence of renal epithelial
cells, providing potential strategies for retarding kidney aging in diabetic nephropathy.
Harmony in health: Innovation for Sustainable Medicine
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