石榴皮提取物在生理和炎症条件下对牙龈来源的间充质基质细胞的基因表达有不同的调节作用。

Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions.

机构信息

Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia.

Medical Faculty Foča, University of East Sarajevo, 73300 Foča, Bosnia and Herzegovina.

出版信息

Int J Mol Sci. 2023 Oct 21;24(20):15407. doi: 10.3390/ijms242015407.

DOI:10.3390/ijms242015407

PMID:37895087

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10607867/

Abstract

Pomegranate has shown a favorable effect on gingivitis/periodontitis, but the mechanisms involved are poorly understood. The aim of this study was to test the effect of pomegranate peel extract (PoPEx) on gingiva-derived mesenchymal stromal cells (GMSCs) under physiological and inflammatory conditions. GMSC lines from healthy (H) and periodontitis (P) gingiva ( = 3 of each) were established. The lines were treated with two non-toxic concentrations of PoPEX (low-10; high-40 µg/mL), with or without additional lipopolysaccharide (LPS) stimulation. Twenty-four genes in GMSCs involved in different functions were examined using real-time polymerase chain reaction (RT-PCR). PoPEx (mostly at higher concentrations) inhibited the basal expression of , , , , , , , and but increased the expression of , , , ratio, , and genes in H-GMSCs. PoPEx increased , , , and but inhibited and gene expression in P-GMSCs. LPS upregulated genes for proinflammatory cytokines and chemokines, tissue regeneration/repair (, , ), and immunomodulation (, , , , ), more strongly in P-GMSCs. PoPEx also potentiated most genes' expression in LPS-stimulated P-GMSCs, including upregulation of osteoblastic genes (, , , and ), simultaneously inhibiting cell proliferation. In conclusion, the modulatory effects of PoPEx on gene expression in GMSCs are complex and dependent on applied concentrations, GMSC type, and LPS stimulation. Generally, the effect is more pronounced in inflammation-simulating conditions.

摘要

石榴对牙龈炎/牙周炎有有益的影响，但其中涉及的机制还不太清楚。本研究的目的是在生理和炎症条件下测试石榴皮提取物（PoPEx）对牙龈来源间充质基质细胞（GMSCs）的作用。从健康（H）和牙周炎（P）牙龈中建立了 GMSC 系（每个条件 3 个）。用两种无毒浓度的 PoPEX（低 10；高 40μg/ml）处理这些细胞系，有或没有额外的脂多糖（LPS）刺激。使用实时聚合酶链反应（RT-PCR）检查 GMSCs 中涉及不同功能的 24 个基因。PoPEx（主要在较高浓度下）抑制 H-GMSCs 中、、、、、和的基础表达，但增加、、比值、、和的表达。PoPEx 增加了 H-GMSCs 中的、、和，但抑制了 P-GMSCs 中的和基因表达。LPS 在上皮细胞来源的趋化因子、组织再生/修复（、、）和免疫调节（、、、）基因的表达，在 P-GMSCs 中上调更强。PoPEx 还增强了 LPS 刺激的 P-GMSCs 中大多数基因的表达，包括上调成骨基因（、、和），同时抑制细胞增殖。总之，PoPEx 对 GMSCs 中基因表达的调节作用是复杂的，取决于所应用的浓度、GMSC 类型和 LPS 刺激。一般来说，在炎症模拟条件下效果更为明显。