TLR4 gene in the regulation of periodontitis and its molecular mechanism

Qi, Weijuan; Yang, Xi; Ye, Ning; Li, Shujun; Han, Qianqian; Huang, Jinyu; Wu, Buling

doi:10.3892/etm.2019.7809

Cited by 15 publications

(16 citation statements)

References 22 publications

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“…TLR4 has been proved to be crucial in periodontitis pathogenesis ( Renn et al, 2018 ). A previous study indicated that TLR4 can remarkably increase inflammatory responses in vivo , and inhibiting TLR4 can significantly improve the symptoms of periodontitis in mice ( Qi et al, 2019 ). Therefore, we conclude that circMAP3K11/miR-511-3p/TLR4 regulatory axis affects the functions of PDLSCs and increases the inflammatory responses in the development of periodontitis.…”

Section: Discussionmentioning

confidence: 99%

CircMAP3K11 Contributes to Proliferation, Apoptosis and Migration of Human Periodontal Ligament Stem Cells in Inflammatory Microenvironment by Regulating TLR4 via miR-511 Sponging

et al. 2021

Front. Pharmacol.

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Growing number of studies regarding the role of circRNAs in the development of various diseases have emerged in recent years, but the role of circRNAs in periodontitis pathogenesis remains obscure. Human periodontal ligament stem cells (hPDLSCs) play a critical role in periodontal remodeling, regeneration and repair processes, and their regenerative capacity could be prohibited in local periodontal inflammatory microenvironment. Herein, we sought to uncover the molecular mechanisms of periodontitis pathogenesis by investigating the role of circMAP3K11 (hsa_circ_002284) for regenerative capacity of hPDLSCs under an inflammatory condition. The hPDLSCs isolated from periodontitis patients were used as a cell model of inflammatory microenvironment to study the effect of the circMAP3K11/miR-511-3p/TLR4 axis on the proliferation, apoptosis and migration of hPDLSCs under inflammatory conditions. Compared to the periodontal tissues from normal subjects, those from periodontitis patients exhibited higher expression levels of circMAP3K11 and TLR4, and lower expression level of miR-511-3p. Both the expressions of circMAP3K11 and TLR4 were negatively correlated with the expressions of miR-511-3p in periodontitis. In vitro studies demonstrated that circMAP3K11 is capable of enhancing hPDLSCs proliferation and migration, and reducing the apoptosis of hPDLSCs. We also found that circMAP3K11 could up-regulate the expression of transcription factors that are closely related to periodontal regeneration (Runx2, OSX, ATF4, and BSP). RT-PCR and western blot showed that the inhibitory role of miR-511-3p on TLR4 expression could be reversed by circMAP3K11, which was in line with the results of bioinformatics tools and luciferase reporter assay. Meanwhile, both in vitro and in vivo studies indicated that circMAP3K11 could reverse the effects of miR-511-3p in periodontitis, which further confirmed that circMAP3K11 functioned as a ‘sponge’ of miR-511-3p to positively regulate the expression of TLR4. Taken together, our study preliminarily uncovered a circMAP3K11/miR-511-3p/TLR4 axis that regulates the function of hPDLSCs in periodontitis, providing novel insight and scientific base in the treatment of periodontal tissue regeneration based on stem cells.

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Section: Discussionmentioning

confidence: 99%

CircMAP3K11 Contributes to Proliferation, Apoptosis and Migration of Human Periodontal Ligament Stem Cells in Inflammatory Microenvironment by Regulating TLR4 via miR-511 Sponging

et al. 2021

Front. Pharmacol.

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“…Previous studies have reported that TLR4 is critical for the activation of NF-κB and the subsequent production of pro-inflammatory cytokines that are implicated in a variety of diseases (19)(20)(21). As a transcription factor, NF-κB serves vital roles in numerous processes, including inflammation, immunity and cell proliferation (22).…”

Section: Discussionmentioning

confidence: 99%

Interleukin‑35 reduces inflammation in acute lung injury through inhibiting TLR4/NF‑κB signaling pathways

Pan

Wang³

et al. 2020

Exp Ther Med

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Acute lung injury (ALI) in children is a complex disease that is accompanied by an inflammatory response. The pathogenesis of ALI in children is not yet well understood. Mice with ALI exhibit inflammation of the lungs and decreased expression of interleukin (IL)-35. To investigate whether the function of IL-35 affects lipopolysaccharide (LPS)-induced ALI, IL-35 was overexpressed in cells. Enzyme-linked immunosorbent assays indicated decreased levels of IL-6 and tumor necrosis factor-α in LPS-induced and agomir-IL-35-treated murine RAW264.7 macrophages. Finally, toll-like receptor 4 (TLR4)/NF-κB signaling pathways were analyzed. The expression of TLR4, NF-κB p65 and NF-κB p50 were decreased, as was the degradation of NF-κB inhibitor-α, in LPS-induced and agomir-IL-35-treated murine RAW264.7 macrophages. The results of the present study demonstrated that IL-35 may exhibit a protective role in ALI by modulating the TLR4/NF-κB signaling pathways.

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“…Th1 cells differentiate from naïve T cells under the influence of the inductive signals IL-12 and IFN-α. In PD, an upregulation of GATA-3 signaling was noted [ 147 ]. GATA-3 was previously reported to suppress STAT4 signaling and thereby limit the differentiation capacity of Th1 cells and in the meantime enhance that of Th2 cells [ 148 ].…”

Section: Oscc Immune Permissive Environment Induced By Periodontal Diseasementioning

confidence: 99%

The Crossroads of Periodontitis and Oral Squamous Cell Carcinoma: Immune Implications and Tumor Promoting Capacities

Elebyary

Barbour

Fine

et al. 2021

Front. Oral. Health

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Periodontitis (PD) is increasingly considered to interact with and promote a number of inflammatory diseases, including cancer. In the case of oral squamous cell carcinoma (OSCC) the local inflammatory response associated with PD is capable of triggering altered cellular events that can promote cancer cell invasion and proliferation of existing primary oral carcinomas as well as supporting the seeding of metastatic tumor cells into the gingival tissue giving rise to secondary tumors. Both the immune and stromal components of the periodontium exhibit phenotypic alterations and functional differences during PD that result in a microenvironment that favors cancer progression. The inflammatory milieu in PD is ideal for cancer cell seeding, migration, proliferation and immune escape. Understanding the interactions governing this attenuated anti-tumor immune response is vital to unveil unexplored preventive or therapeutic possibilities. Here we review the many commonalities between the oral-inflammatory microenvironment in PD and oral-inflammatory responses that are associated with OSCC progression, and how these conditions can act to promote and sustain the hallmarks of cancer.

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TLR4 gene in the regulation of periodontitis and its molecular mechanism

Cited by 15 publications

References 22 publications

CircMAP3K11 Contributes to Proliferation, Apoptosis and Migration of Human Periodontal Ligament Stem Cells in Inflammatory Microenvironment by Regulating TLR4 via miR-511 Sponging

CircMAP3K11 Contributes to Proliferation, Apoptosis and Migration of Human Periodontal Ligament Stem Cells in Inflammatory Microenvironment by Regulating TLR4 via miR-511 Sponging

Interleukin‑35 reduces inflammation in acute lung injury through inhibiting TLR4/NF‑κB signaling pathways

The Crossroads of Periodontitis and Oral Squamous Cell Carcinoma: Immune Implications and Tumor Promoting Capacities

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