Network pharmacology modeling identifies synergistic interaction of therapeutic and toxicological mechanisms for Tripterygium hypoglaucum Hutch

Zhang, Dan; Dong, Yizhu; Lv, Jintao; Zhang, Bing; Zhang, Xiaomeng; Lin, Zhijian

doi:10.1186/s12906-021-03210-8

Cited by 2 publications

(1 citation statement)

References 92 publications

(88 reference statements)

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“…28 Two different network pharmacology studies suggest that the PI3K/AKT pathway is linked to the effectiveness of hydroxychloroquine and tripterygium hypoglaucum as treatments for SLE. 29,30 Furthermore, Jie Wang et al demonstrated that azithromycin could enhance the alternatively activated macrophage phenotype to alleviate SLE via the PI3K/AKT pathway. 31 In SLE, the PI3K/ AKT pathway also contributes to the progression of organ damage.…”

Section: Discussionmentioning

confidence: 99%

Reduced miR-99a-3p levels in systemic lupus erythematosus may promote B cell proliferation via NCAPG and the PI3K/AKT signaling pathway

Zhu,

Zhou,

Yang

et al. 2024

Lupus

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Background Systemic lupus erythematosus is an immunologically dysregulated disease characterized by the presence of multiple autoantibodies. In SLE, B lymphocytes contribute to the dysregulated production of autoantibodies and cytokines. Recently, we discovered that miR-99a-3p binds to both EIF4EBP1 and NCAPG mRNA and that lowering miR-99a-3p can promote B cell autophagy in SLE by increasing EIF4EBP1 expression. However, the functions of miR-99a-3p and NCAPG in SLE have not been extensively investigated. Objective This work aims to evaluate the levels of miR-99a-3p and NCAPG expression in SLE B cells and to determine whether the aberrant expression of miR-99a-3p and NCAPG contributes to the pathological mechanisms in SLE. Methods B lymphocytes were obtained through immunomagnetic negative selection. Using RT-qPCR, miR-99a-3p and NCAPG mRNA expressions in B lymphocytes and in the BALL-1 cell line were measured. To determine the relative abundance of NCAPG, PI3K, p-PI3K, AKT, and p-AKT, we normalize them to the level of β-actin using Western blotting. Evaluation of miR-99a-3p and NCAPG’s impact on cell proliferation was done utilizing CCK-8 assay. Using flow cytometry, the cell cycle and apoptosis were both measured. Results Comparing SLE B cells to healthy controls, miR-99a-3p expression was significantly downregulated. Additionally, it was observed that SLE B cells had significantly higher NCAPG mRNA expression. Blocking miR-99a-3p expression in BALL-1 cells with an antagomir elevated NCAPG expression, facilitated PI3K/AKT pathway activation, improved cell proliferation, raised the fraction of S-phase cells, and prevented cell apoptosis. The opposite effects of upregulated miR-99a-3p levels on BALL-1 cells were observed by using an agomir. Furthermore, the effect of decreased miR-99a-3p expression on cell proliferation was partially mediated by elevating NCAPG levels and activating the PI3K/AKT pathway. Conclusion Our research indicates that lower miR-99a-3p expression in SLE B cells appears to boost B cell number via the NCAPG and PI3K/AKT pathways.

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