Abstract
Background
Recent years of evidence suggest the crucial role of renal tubular cells in developing diabetic kidney disease. Scopoletin (SCOP) is a plant-based coumarin with numerous biological activities. This study aimed to determine the effect of SCOP on renal tubular cells in developing diabetic kidney disease and to elucidate mechanisms.
Methods and results
In this study, SCOP was evaluated in vitro using renal proximal tubular (HK-2) cells under hyperglycemic conditions to understand its mechanism of action. In HK-2 cells, SCOP alleviated the high glucose-generated reactive oxygen species (ROS), restored the levels of reduced glutathione, and decreased lipid peroxidation. High glucose-induced alteration in the mitochondrial membrane potential was markedly restored in the SCOP-treated cells. Moreover, SCOP significantly reduced the high glucose-induced apoptotic cell population in the Annexin V-FITC flow cytometry study. Furthermore, high glucose markedly elevated the mRNA expression of fibrotic and extracellular matrix (ECM) components, namely, transforming growth factor (TGF)-β, alfa-smooth muscle actin (α-SMA), collagen I, and collagen III, in HK-2 cells compared to the untreated cells. SCOP treatment reduced these mRNA expressions compared to the high glucose-treated cells. Collagen I and TGF-β protein levels were also significantly reduced in the SCOP-treated cells. Further findings in HK-2 cells revealed that SCOP interfered with the epithelial-mesenchymal transition (EMT) in the high glucose-treated HK-2 cells by normalizing E-cadherin and downregulating the vimentin and α-SMA proteins.
Conclusions
In conclusion, SCOP modulates the high glucose-generated renal tubular cell oxidative damage and accumulation of ECM components and may be a promising molecule against diabetic nephropathy.
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Data availability
The data will be made available from the corresponding author on reasonable request.
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Funding
This study was supported by the Indian Council of Medical Research (ICMR) (Grant No. 5/7/1762/CH/Adhoc/RBMCH-2021), Ministry of Health and Family Welfare, Government of India and the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India.
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Sourav Kundu and Sitara Ghosh: Performed all experiments and methodology, prepared figures, and wrote the main manuscript. Bidya Dhar Sahu: Supervision, Funding acquisition, resources, Edited final manuscript.
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Kundu, S., Ghosh, S. & Sahu, B.D. Scopoletin alleviates high glucose-induced toxicity in human renal proximal tubular cells via inhibition of oxidative damage, epithelial-mesenchymal transition, and fibrogenesis. Mol Biol Rep 51, 620 (2024). https://doi.org/10.1007/s11033-024-09579-2
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DOI: https://doi.org/10.1007/s11033-024-09579-2