AI Article Synopsis
- Chronic kidney diseases often progress to end-stage renal disease, making the study of effective treatments crucial, particularly for addressing kidney fibrosis and epithelial-to-mesenchymal transition (EMT).
- This research investigates kaempferol (KAE), a plant-derived flavonoid, focusing on its effects on tissue and function in kidney disease models, including its ability to alter extracellular matrix deposition and cellular behavior.
- Findings indicate that KAE reduces blood pressure and key fibrosis markers in hypertensive rats, and it inhibits cell proliferation and migration in human kidney cells, suggesting it may be a beneficial therapeutic agent for managing kidney fibrosis and EMT.
Article Abstract
Background: Most chronic kidney diseases (CKDs) develop to end-stage renal disease (ESRD), which is characterized by fibrosis and permanent tissue and function loss. As a result, better and more effective remedies are essential. Kaempferol (KAE) is a common flavonoid extracted from plants. It can control the progression of kidney fibrosis and the epithelial-to-mesenchymal transition (EMT) of the renal tubular system.
Purpose: We aim to investigate the effect of KAE therapy on extracellular matrix deposition and stimulation of EMT in vitro and in vivo to elucidate the treatment mechanisms regulating these effects.
Study Design: Chronic hypertension-induced kidney fibrosis was studied in spontaneously hypertensive rats with chronic kidney disease. Biochemical analysis, histological staining, and the expression level of relative proteins were used to assess the effect of KAE on renal function and fibrosis. The direct impact of KAE on proliferation and migration was evaluated using human renal tubular epithelial cells (HK-2) induced by transforming growth factor-β1 (TGF-β1), which can then induce EMT. The molecular mechanism of KAE was verified using co-IP assay and immunofluorescence.
Results: KAE could reduce blood pressure and decrease the extracellular matrix (ECM) components (including collagen I and collagen Ш), TGF-β1, and α-SMA in the kidneys of hypertension-induced rats with chronic kidney disease. Moreover, in HK-2 cell treated with TGF-β1, KAE administration significantly suppressed proliferation, migration, and EMT via increasing the expression of E-cadherin, while reducing the N-cadherin and α-SMA. Sufu was exceedingly repressed in HK-2 cells treated with TGF-β1. KAE inhibited the activation of Shh and Gli through increasing the expression of Sufu, thereby blocking the nuclear translocation of Gli1 in vitro.
Conclusion: KAE ameliorated kidney fibrosis and EMT by inhibiting the sonic hedgehog signaling pathway, thereby to attenuate the pathological progression of hypertensive kidney fibrosis.
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| http://dx.doi.org/10.1016/j.phymed.2022.154246 | DOI Listing |
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