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人牙髓细胞中PPAR/的研究:一项初步体外研究。

Investigation of PPAR/ within Human Dental Pulp Cells: A Preliminary In Vitro Study.

作者信息

de Lima Caroline L, Amorim Bruna R, Royer Carine, Resende Augusto P, Borin Maria F, Neves Francisco A R, Acevedo Ana Carolina

机构信息

Laboratory of Oral Histopathology, Faculty of Health Sciences, University of Brasilia, University Campus Darcy Ribeiro, Brasília, Brazil.

Laboratory of Molecular Pharmacology, Faculty of Health Sciences, University of Brasilia, University Campus Darcy Ribeiro, Brasília, Brazil.

出版信息

PPAR Res. 2021 Mar 18;2021:8854921. doi: 10.1155/2021/8854921. eCollection 2021.

Abstract

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 (PPAR/) 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 PPAR/ expression and assessed the anti-inflammatory effects evoked by activation of PPAR/ in lipopolysaccharide- (LPS-) induced hDPCs. Our results showed that hDPCs constitutively expressed PPAR/ mRNA/protein, and treatment with LPS increased mRNA expression. The selective PPAR/ agonist GW0742 significantly decreased inflammation-related mRNA expression in hDPCs (, , , , and ) and RAW264.7 cells ( and ). Further, PPAR/ 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 PPAR/. In addition, they suggest that activation of PPAR/ 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.

摘要

控制炎症反应以恢复组织稳态是从龋损牙组织清除病原体后维持牙齿活力的关键步骤。核过氧化物酶体增殖物激活受体β/δ(PPAR/)是一种配体激活的转录因子,在许多细胞和组织中具有新出现的抗炎作用。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PPAR/的表达,并评估了PPAR/激活在脂多糖(LPS)诱导的hDPCs中所引发的抗炎作用。我们的结果表明,hDPCs组成性表达PPAR/ mRNA/蛋白,LPS处理可增加mRNA表达。选择性PPAR/激动剂GW0742显著降低hDPCs(、、、、和)和RAW264.7细胞(和)中炎症相关mRNA的表达。此外,PPAR/激动剂减弱了hDPCs中MMP2/9的明胶酶活性。先前经LPS处理的hDPCs通过Transwell共培养系统的膜增加了RAW264.7细胞的迁移。相反,用GW0742预处理显著减少了巨噬细胞的募集。这些发现首次提供了hDPCs表达PPAR/的证据。此外,它们表明GW0742激活PPAR/可减弱一些与炎症过程相关的体外细胞和分子方面的变化,指出有必要研究其在牙髓炎症中的潜在靶向作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f19/7997762/6fe8a1cbe320/PPAR2021-8854921.001.jpg

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