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.

Graphical abstract

中文翻译：

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原人参二醇通过调节 PTX3/MAPK/ERK1/2 通路改善狼疮性肾炎

摘要

狼疮性肾炎 (LN) 是系统性红斑狼疮 (SLE) 影响肾脏后发生的一种肾脏疾病。Pentraxin 3 (PTX3) 在 LN 患者的血清中高表达。肾脏PTX3沉积与蛋白尿、炎症等临床症状直接相关。系膜细胞（MCs）过度增殖是LN进展过程中代表性的病理改变之一，与其发病机制密切相关。原人参二醇(PPD)是人参皂苷代谢的主要成分，在LN中尚未见报道。本研究的目的是探讨PTX3与系膜细胞增殖之间的关系，并评估PPD在改善LN中的潜在作用和机制。PTX3在LN患者和LN小鼠的肾脏中高表达，并与蛋白尿和PCNA等肾脏病理指标呈正相关。PTX3的过度表达促进MCs的增殖，促进MAPK/ERK1/2信号通路的激活，并增加HIF-1α的表达。进一步研究表明，PPD能有效抑制高表达PTX3的MCs的异常增殖，并显着改善MRL/lpr小鼠的蛋白尿等LN症状。其机制可能与抑制PTX3/MAPK/ERK1/2通路有关。本研究中，体外、体内和临床样本结果均表明PTX3参与MCs增殖的调节和LN的早期发生。天然活性化合物PPD可以通过调节PTX3/MAPK/ERK1/2通路来改善LN。

图形概要