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Protopanaxadiol improves lupus nephritis by regulating the PTX3/MAPK/ERK1/2 pathway

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Abstract

Lupus nephritis (LN) is a kidney disease that occurs after systemic lupus erythematosus (SLE) affects the kidneys. Pentraxin 3 (PTX3) is highly expressed in the serum of patients with LN. Renal PTX3 deposition is directly related to clinical symptoms such as proteinuria and inflammation. The excessive proliferation of mesangial cells (MCs) is one of the representative pathological changes in the progression of LN, which is closely related to its pathogenesis. Protopanaxadiol (PPD) is the main component of ginsenoside metabolism and has not been reported in LN. The aim of this study was to investigate the relationship between PTX3 and mesangial cell proliferation and to evaluate the potential role and mechanism of PPD in improving LN. PTX3 is highly expressed in the kidneys of LN patients and LN mice and is positively correlated with renal pathological indicators, including proteinuria and PCNA. The excessive expression of PTX3 facilitated the proliferation of MCs, facilitated the activation of the MAPK/ERK1/2 signaling pathway, and increased the expression of HIF-1α. Further studies showed that PPD can effectively inhibit the abnormal proliferation of MCs with high expression of PTX3 and significantly improve LN symptoms such as proteinuria in MRL/lpr mice. The mechanism may be related to the inhibition of the PTX3/MAPK/ERK1/2 pathway. In this study, both in vitro, in vivo, and clinical sample results show that PTX3 is involved in the regulation of MCs proliferation and the early occurrence of LN. Natural active compound PPD can improve LN by regulating the PTX3/MAPK/ERK1/2 pathway.

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Acknowledgements

We thank the support from Yantai University and Yu-Huang-Ding Hospital/Qingdao University.

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  1. Zhenyuan Li and Hailin Gan have contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, No. 32 Qingquan Road, Laishan District, Yantai, 264005, Shandong, People’s Republic of China

    Zhenyuan Li, Hailin Gan, Kai Ji, Mingyan Yang, Tao Pan, Xiangting Meng, Teng Liu, Zhixia Wang, Baifang Gong & Huaying Fan

  2. Department of Nephrology, Yu‐Huang‐Ding Hospital/Qingdao University, No. 20 Yuhuangding East Road, Zhifu District, Yantai, 264000, Shandong Province, People’s Republic of China

    Dong Qi

  3. Shandong Boyuan Biomedical Co., Ltd, Yantai, 264003, People’s Republic of China

    Ke Liu

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Contributions

HF, ZL, and DQ conceived and designed research; HG, KJ, MY, TP, XM, TL, ZW, BG, and KL performed experiments; ZL, HG, and KJ analyzed data; MY, TP, XM, TL, KL, and ZW interpreted results of experiments; ZL and HG drafted the manuscript; HF, ZL, and MY edited and revised the manuscript; HF and DQ approved the final version of the manuscript.

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Correspondence to Dong Qi or Huaying Fan.

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Li, Z., Gan, H., Ji, K. et al. Protopanaxadiol improves lupus nephritis by regulating the PTX3/MAPK/ERK1/2 pathway. J Nat Med (2024). https://doi.org/10.1007/s11418-023-01777-9

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