人牙髓细胞中PPARβ/δ的初步体外研究

IF 3.5 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL PPAR Research Pub Date : 2021-03-18 eCollection Date: 2021-01-01 DOI:10.1155/2021/8854921
Caroline L de Lima, Bruna R Amorim, Carine Royer, Augusto P Resende, Maria F Borin, Francisco A R Neves, Ana Carolina Acevedo
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引用次数: 0

摘要

控制炎症反应以恢复组织稳态是去除龋病后维持牙齿活力的关键步骤。核过氧化物酶体增殖体激活受体β/δ (PPARβ/δ)是一种配体激活的转录因子,在许多细胞和组织中具有新兴的抗炎作用。然而,其在人牙髓细胞(hDPCs)中的表达和功能尚不清楚。因此,本研究评估了PPARβ/δ在脂多糖(LPS)诱导的hDPCs中的表达,并评估了激活PPARβ/δ所引起的抗炎作用。结果表明,hDPCs组成性表达PPARβ/δ mRNA/蛋白,LPS处理增加了PPARβ/δ mRNA的表达。选择性PPARβ/δ激动剂GW0742显著降低hDPCs (IL6、IL1β、TNFα、MMP1和MMP2)和RAW264.7细胞(IL6和TNFα)炎症相关mRNA表达。此外,PPARβ/δ激动剂降低了hDPCs中MMP2/9凝胶溶解活性。先前lps条件下的hDPCs增加了RAW264.7细胞通过Transwell共培养系统膜的迁移。相反,GW0742预处理显著降低巨噬细胞募集。这些发现为hDPCs表达PPARβ/δ提供了首批证据。此外,他们认为GW0742激活PPARβ/δ可以在体外减弱与炎症过程相关的一些细胞和分子方面,并指出其在牙髓炎症中的潜在靶点作用。
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Investigation of PPARβ/δ within Human Dental Pulp Cells: A Preliminary In Vitro Study.

Controlling the inflammatory response to restore tissue homeostasis is a crucial step to maintain tooth vitality after pathogen removal from caries-affected dental tissues. The nuclear peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is a ligand-activated transcription factor with emerging anti-inflammatory roles in many cells and tissues. However, its expression and functions are poorly understood in human dental pulp cells (hDPCs). Thus, this study evaluated PPARβ/δ expression and assessed the anti-inflammatory effects evoked by activation of PPARβ/δ in lipopolysaccharide- (LPS-) induced hDPCs. Our results showed that hDPCs constitutively expressed PPARβ/δ mRNA/protein, and treatment with LPS increased PPARβ/δ mRNA expression. The selective PPARβ/δ agonist GW0742 significantly decreased inflammation-related mRNA expression in hDPCs (IL6, IL1β, TNFα, MMP1, and MMP2) and RAW264.7 cells (Il6 and Tnfα). Further, PPARβ/δ agonist attenuated MMP2/9 gelatinolytic activity in hDPCs. Previously LPS-conditioned hDPCs increased the migration of RAW264.7 cells through the membrane of a Transwell coculture system. Conversely, pretreatment with GW0742 markedly decreased macrophage recruitment. These findings provide among the first evidence that hDPCs express PPARβ/δ. In addition, they suggest that activation of PPARβ/δ by GW0742 can attenuate some cellular and molecular in vitro aspects related to the inflammatory process, pointing out to investigate its potential target role in dental pulp inflammation.

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来源期刊
PPAR Research
PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.20
自引率
3.40%
发文量
17
审稿时长
12 months
期刊介绍: PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.
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