Pulchinenoside A downregulates LRP1 to inhibit the proliferation， migration， and invasion of synovial inflammatory cells
10.19405/j.cnki.issn1000–1492.2026.09.010
- VernacularTitle:白头翁皂苷A下调LRP1抑制滑膜炎性细胞的增殖、迁移和侵袭
- Author:
Lifang MAO
1
;
Tianyu CHEN
1
;
Jinhong WANG
1
;
Hao WANG
1
;
Yingjie ZHAO
1
;
Renpeng ZHOU
1
;
Wei HU
1
;
Chao LU
1
Author Information
1. School of Pharmaceutical Sciences， Anhui Medical University， Hefei 230032
- Publication Type:Journal Article
- Keywords:
pulchinenoside A;
SW982 synovial cells;
TNF-α;
migration;
invasion;
RAP
- From:
Acta Universitatis Medicinalis Anhui
2026;61(9):1584-1593
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects and mechanisms of pulchinenoside A （PSA） on tumor necrosis factor-α （TNF-α） -induced abnormal proliferation， migration， and invasion of synovial fibroblasts. MethodsA synovitis model was established by stimulating SW982 synovial cells with TNF-α. The low-density lipoprotein receptor-related protein 1 （LRP1） was knocked down using LRP1-specific siRNA or inhibited by the receptor-associated protein （RAP）. Cells were treated with various concentrations of PSA， and cell viability was assessed by CCK-8 assay. Protein levels of LRP1， matrix metalloproteinase-3 （MMP3）， and N-cadherin were measured by Western blotting. Proliferation was evaluated using an EdU incorporation assay. Migration and invasion capacities were examined by Transwell and wound-healing assays. mRNA expression of LRP1， MMP3， N-cadherin， IL-1β， IL-6， and TNF-α was detected by reverse transcription quantitative real-time PCR （RT-qPCR）. Immunofluorescence staining was used to visualize the expression of MMP3 and N-cadherin. The involvement of LRP1 was further verified with the inhibitor RAP. ResultsCompared with the TNF-α-treated model group， PSA treatment significantly reduced SW982 cell viability （P<0.05）， downregulated MMP3 and N-cadherin expression （both P<0.01）， and decreased the proportion of EdU-positive cells （P<0.05）. Moreover， TNF-α stimulation upregulated LRP1 expression compared with normal controls （P<0.01）， whereas PSA treatment reversed this increase （P<0.05）. LRP1 knockdown or inhibition markedly decreased MMP3 and N-cadherin levels compared with the model group （both P<0.01）. Similarly， the combination of PSA and RAP led to significant reductions in MMP3 and N-cadherin expression compared with the model group （both P<0.01）. ConclusionPSA inhibits TNF-α-induced abnormal proliferation， migration， and invasion of synovial， at least in part， by downregulating LRP1 expression.
