Abstract
Background
Chronic renal failure (CRF) is the result of kidney damage. Puerarin is a flavonoid with specific nephroprotective effect, but its effect on CRF needs further research. This study explored the effect of puerarin on CRF and the potential molecular mechanism.
Methods
Adenine was used to establish an in vivo CRF model in rats, and rats were intragastrically administered with puerarin at a dose of 400 mg/kg body weight once a day from day 1 to day 28. Hematoxylin and eosin (HE) and Masson staining were used to observe the morphology and fibrosis of kidney tissue. Lipopolysaccharide (LPS) (400 ng/mL)/H2O2 (200 µM) was applied to human kidney 2 (HK-2) cells to construct an in vitro CRF model. Enzyme-linked immunosorbent assay (ELISA) was performed to validate interleukin (IL)-1β and IL-18 levels. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to detect microRNA (miR)-342-3p levels. Transforming growth factor beta (TGF-β)1, SMAD2, SMAD3, and pyroptosis marker proteins were detected by Western blot. The interaction between miR-342-3p and TGF-β/SMAD was determined by a dual-luciferase reporter gene assay. Cell Counting Kit-8 (CCK-8) assay was utilized to determine cell viability.
Results
In the CRF model, puerarin alleviated renal injury and fibrosis and reduced creatinine (Cr) and blood urea nitrogen (BUN) levels. At the same time, miR-342-3p was downregulated, while the TGF-β/SMAD axis was activated and levels of IL-1β and IL-18 were increased. After treatment of CRF rats with puerarin, the expression level of miR-342-3p was increased, the TGF-β/SMAD axis was inhibited, and the secretion of IL-1β and IL-18 was decreased. MiR-342-3p directly bound to and negatively regulated the expression of TGF-β1, SMAD2, and SMAD3. In the in vitro CRF model, miR-342-3p inhibited HK-2 cell pyroptosis by inhibiting the TGF-β/SMAD axis.
Conclusion
Puerarin reduced renal injury and pyroptosis in CRF rats by targeting the miR-342-3p/TGF-β/SMAD axis.
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Data availability
The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This study was supported by Medical Discipline Leader Training Program of Health Commission of Yunnan Province in 2019 (Grant Number D-2019015); 2023 Yunnan Provincial Department of Science and Technology-Kunming Medical University Applied Basic Research Joint Special Fund General Project (Project number: 202301AY070001-154)； Regional Project of National Natural Science Foundation of China (Grant Number 82160142) in 2022； Outstanding Youth Cultivation Project of Applied Basic Research Joint Special Fund of Yunnan Provincial Department of Science and Technology and Kunming Medical University in 2022 (Grant Number 202201AY070001-044).
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Contributions: (I) Conception and design: JY and WF; (II) Administrative support: WF; (III) Provision of study materials or patients: BL; (IV) Collection and assembly of data: JW; (V) Data analysis and interpretation: JY and BL; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
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The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Animal experiments were performed under a project license (No. kmmu20221002) granted by ethics board of the First Affiliated Hospital of Kunming Medical University, in compliance with The First Affiliated Hospital of Kunming Medical University guidelines for the care and use of animals.
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Yang, J., Li, B., Wang, J. et al. Puerarin alleviates chronic renal failure-induced pyroptosis in renal tubular epithelial cells by targeting miR-342-3p/TGF-β/SMAD axis. Genes Genom 45, 1563–1573 (2023). https://doi.org/10.1007/s13258-023-01448-9
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DOI: https://doi.org/10.1007/s13258-023-01448-9