HIF1α/PLD2 axis linked to glycolysis induces T-cell immunity in oral lichen planus

Wang, Fang; Zhou, Gang

doi:10.1016/j.bbagen.2020.129602

Cited by 6 publications

(10 citation statements)

References 32 publications

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“…Wang et al (34) reported that the PLD2/MTOR/HIF-1α signal might play an important role in immune dysfunction in OLP patients. It has also been reported that PLD2 is highly expressed in OLP, and PLD2 promotes T-cell proliferation and pro-inflammatory phenotype differentiation in OLP (35). Additionally, 6 immune-related signal pathways were enriched, which suggests that abnormally expressed circRNAs may be involved in regulating the immune process.…”

Section: Discussionmentioning

confidence: 83%

Expression profile of circular RNAs in oral lichen planus

Song¹,

Xu²,

Shao³

et al. 2021

Ann Palliat Med

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Background: This study sought to identify the circular RNAs (circRNAs) differentially expressed in oral lichen planus (OLP) to investigate the possible role of circRNAs in this disease's pathogenesis.Methods: Six OLP and six normal oral mucosal tissues were used for circRNA detection and sequencing.10 selected circRNAs were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to predict the functions of circRNAs in OLP. TargetScan and miRanda were applied to predict targeted micro (mi)RNAs and messenger (m)RNAs of circRNAs, and competing endogenous (ce)RNA networks were mapped.Results: One hundred and thirty-five circRNAs were identified differentially expressed in OLP tissues compared to normal control tissues, including 83 upregulated circRNAs, and 52 down-regulated circRNAs.RT-qPCR confirmed that 10 circRNAs were all abnormally expressed in OLP. The GO functional analysis and KEGG pathway analysis showed that differentially expressed circRNAs were involved in 535 GO functional items and 78 signal pathways. A ceRNA network analysis showed that circRNAs might interact with a variety of miRNAs.Conclusions: This study mapped the expression profile of abnormally expressed circRNAs in OLP tissues for the first time and showed that circRNAs appear to play an important role in the pathogenesis of OLP.

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Section: Discussionmentioning

confidence: 83%

Expression profile of circular RNAs in oral lichen planus

Song¹,

Xu²,

Shao³

et al. 2021

Ann Palliat Med

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“…25 Our previous findings revealed that the activation of mTOR pathway in T cells varied with glucose concentration, demonstrating mTOR serves as an important metabolic sensor. 9 Besides, inhibition of mTOR pathway could reduce the expression of Hif1α in T cells, 14 which is a major transcriptional regulator of LDHA. Either downregulation of mTOR or Hif1α could lead to the inhibition of LDHA.…”

Section: -Dg Is Considered As An Inhibitor Of Glucose Metabolismmentioning

confidence: 99%

“…Moreover, molecular pathways, including mammalian target of rapamycin (mTOR), hypoxia‐inducible factor 1α (HIF1α) and phospholipase D2 (PLD2), motivate glycolytic metabolism in T cells 11–13 . We have found that the expression of p‐mTOR, HIF1α and PLD2 was elevated in peripheral or local T cells of OLP, and mTOR/HIF1α/PLD2 axis could upregulate the phosphorylation of LDHA in T cells 9,14,15 . Besides, mTOR pathway could dynamically respond to extracellular glucose signals, then correspondingly regulate T‐cell glycolysis, and finally support T‐cell proliferation and differentiation 9 .…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13] We have found that the expression of p-mTOR, HIF1α and PLD2 was elevated in peripheral or local T cells of OLP, and mTOR/HIF1α/PLD2 axis could upregulate the phosphorylation of LDHA in T cells. 9,14,15 Besides, mTOR pathway could dynamically respond to extracellular glucose signals, then correspondingly regulate T-cell glycolysis, and finally support Tcell proliferation and differentiation. 9 These findings suggested that deregulated mTOR pathway might disturb the glycolytic metabolism in T cells, thereby leading to the dysfunctional immunity of OLP.…”

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confidence: 99%

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2‐Deoxy‐D‐glucose impedes T cell–induced apoptosis of keratinocytes in oral lichen planus

Wang

Zhang

Zhou

2021

J Cellular Molecular Medi

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Oral lichen planus (OLP) is a chronic inflammatory immune disease of unknown aetiology and has been recognized as an oral potentially malignant disorder (OPMD). 1,2 The typically histopathological characteristics of OLP are dense subepithelial infiltration of lymphocytes and liquefactive degeneration in the basal keratinocytes. 2 T cell-mediated dysfunctional immunity has been widely supposed to be the main pathogenesis of OLP. 3,4 Our previous studies demonstrated that Th1-biased responses participated in the development of OLP. 5,6 Specifically, T helper (Th) cells are activated after antigen presentation by major histocompatibility complex II (MHC-II) molecules and then produce pro-inflammatory cytokines, including interferonγ (IFNγ) and interleukin-2 (IL-2). 4 These cytokines together with MHC-I molecules on keratinocytes activate cytotoxic T cells, which further induce the apoptosis of keratinocytes. 4 The metabolic reprogramming in T-cell immune responses is characterized by a switch to aerobic glycolysis, also known as 'Warburg effect' that was first described in cancer. 7 Blocking aerobic glycolysis is pernicious to proliferation and differentiation of effector T cells

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“…Wang et al confirmed that the mTOR pathway played a vital role in the immunometabolism of T lymphocytes in OLP patients 9 . The HIF1α/PLD2 axis was enriched in OLP lesions, which was thought to be a key regulatory signaling pathway involving T-lymphocyte immunity by promoting T-lymphocyte proliferation and pro-inflammatory phenotype differentiation of OLP 10 , 11 . Various inflammation-related cytokines from OLP patients, including interleukins (ILs) 12 , 13 , transforming growth factor-β (TGF-β) 14 , interferon-γ (IFN-γ) 15 and tumor necrosis factor-α (TNF-α) 16 , have been shown to play an important role in immune disorders.…”

Section: Introductionmentioning

confidence: 99%

Reveals of quercetin’s therapeutic effects on oral lichen planus based on network pharmacology approach and experimental validation

Zhao

Ling-lin

Zhang

et al. 2022

Sci Rep

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Oral lichen planus (OLP) is a localized autoimmune disease of the oral mucosa, with an incidence of up to 2%. Although corticosteroids are the first-line treatment, they cause several adverse effects. Quercetin, a naturally occurring compound, has fewer side-effects and provides long-term benefits. Besides, it has powerful anti‑inflammatory activities. Here, we combined network pharmacology with experimental verification to predict and verify the key targets of quercetin against OLP. First, 66 quercetin-OLP common targets were analyzed from various databases. The protein–protein interaction (PPI) network was constructed. Topology analysis and MCODE cluster analysis of common targets were conducted to identify 12 key targets including TP53, IL-6 and IFN-γ and their connections. Gene functions and key signaling pathways, including reactive oxygen species metabolism, IL-17 pathway and AGE-RAGE pathway, were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, in vitro experiments showed that quercetin interfered with Th1/Th2 balance by acting on IL-6 and IFN-γ to modulate the immune system in treating OLP. Quercetin considerably affected the apoptosis and migration of T lymphocytes in OLP patients. Our study reveals the potential therapeutic targets and signaling pathways of quercetin associated with OLP, and establishes the groundwork for future clinical applications.

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HIF1α/PLD2 axis linked to glycolysis induces T-cell immunity in oral lichen planus

Cited by 6 publications

References 32 publications

Expression profile of circular RNAs in oral lichen planus

Expression profile of circular RNAs in oral lichen planus

2‐Deoxy‐D‐glucose impedes T cell–induced apoptosis of keratinocytes in oral lichen planus

Reveals of quercetin’s therapeutic effects on oral lichen planus based on network pharmacology approach and experimental validation

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