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Liquiritin inhibits TGF-β1-induced epithelial mesenchymal transition and extracellular matrix deposition in human renal proximal tubular epithelial cells by suppressing the MAPK signaling

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Abstract

Background

Excessive extracellular matrix (ECM) deposition leads to renal fibrosis, a typical hallmark of chronic kidney disease. Liquiritin is a flavonoid extracted from the rhizome part of Glycyrrhiza glabra and has anti-fibrotic and nephroprotective effects. However, its role and underlying mechanism in renal fibrosis remain unknown.

Methods

Human renal proximal tubular epithelial cells (HRPTEpiCs) were stimulated with 10 ng/mL TGF-β1 to induce renal fibrosis models in vitro. The morphology of HRPTEpiCs was observed under a light microscope. CCK-8 was utilized to test cell viability. Immunofluorescence staining was conducted to measure α-SMA expression in HRPTEpiCs. RT-qPCR was used to assess relative mRNA expression. The protein levels of ECM markers, epithelial mesenchymal transition (EMT) markers, and MAPK signaling-related molecules in HRPTEpiCs were tested using western blotting.

Results

TGF-β1-treated HRPTEpiCs showed a fibroblast-like morphology, and the morphology of HRPTEpiCs was restored by liquiritin. Liquiritin suppressed TGF-β1-stimulated ECM deposition and EMT process in HRPTEpiCs. Additionally, liquiritin repressed TGF-β1-induced MAPK signaling activation in HRPTEpiCs.

Conclusion

Liquiritin mitigates TGF-β1-triggered EMT process and ECM deposition in HRPTEpiCs by inactivating MAPK signaling, thus preventing renal fibrosis.

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Data availability

The datasets analyzed or used during the current study are available from corresponding author on reasonable request.

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Acknowledgments

The work was supported by Wuhan Municipal Health Commission Medical Research Fund, Youth Project (Approval number: WX20Q21).

Funding

The work was supported by Wuhan Municipal Health Commission Medical Research Fund, Youth Project (Approval number: WX20Q21).

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Author notes

  1. Zhen Chen and Yi jue Liu have equally contributed to the work.

Authors and Affiliations

  1. Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 26 Shengli Street, Jiang’an District, Wuhan, 430014, Hubei, China

    Zhen Chen, Yi jue Liu, Bo Yu, Wei Li, Mengli Zhang, Xian Wu, Feng Gui, Huan Peng & Fen Ai

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  1. Zhen Chen
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  2. Yi jue Liu
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  4. Wei Li
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Contributions

ZC and YL conceived and designed the experiments. ZC, YL, BY, WL, MZ, XW, FG, HP and FA carried out the experiments. ZC, YL, FG, HP, and FA analyzed the data. ZC, YL, FG, HP and FA drafted the manuscript. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript.

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Correspondence to Feng Gui, Huan Peng or Fen Ai.

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Chen, Z., Liu, Y.j., Yu, B. et al. Liquiritin inhibits TGF-β1-induced epithelial mesenchymal transition and extracellular matrix deposition in human renal proximal tubular epithelial cells by suppressing the MAPK signaling. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00377-8

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