The role of Nrf2 in periodontal disease by regulating lipid peroxidation, inflammation and apoptosis

Ma, Fengyu; Luo, Shangdie; Lu, Chen; Jiang, Xinrong; Chen, Kexiao; Deng, Jianwen; Ma, Shuyuan; Li, Zejian

doi:10.3389/fendo.2022.963451

Cited by 19 publications

(5 citation statements)

References 121 publications

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“…Furthermore, the previous study showed that Keap1 acts as a negative regulator of the Nrf2 pathway [ 29 ]. Therefore, we investigated whether echinatin has a direct interaction with Keap1, leading to the activation of the Nrf2-HO-1 signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

Echinatin attenuates acute lung injury and inflammatory responses via TAK1-MAPK/NF-κB and Keap1-Nrf2-HO-1 signaling pathways in macrophages

Luo,

Wang,

Xiong

et al. 2024

PLoS ONE

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Echinatin is an active ingredient in licorice, a traditional Chinese medicine used in the treatment of inflammatory disorders. However, the protective effect and underlying mechanism of echinatin against acute lung injury (ALI) is still unclear. Herein, we aimed to explore echinatin-mediated anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated ALI and its molecular mechanisms in macrophages. In vitro, echinatin markedly decreased the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated murine MH-S alveolar macrophages and RAW264.7 macrophages by suppressing inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) expression. Furthermore, echinatin reduced LPS-induced mRNA expression and release of interleukin-1β (IL-1β) and IL-6 in RAW264.7 cells. Western blotting and CETSA showed that echinatin repressed LPS-induced activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways through targeting transforming growth factor-beta-activated kinase 1 (TAK1). Furthermore, echinatin directly interacted with Kelch-like ECH-associated protein 1 (Keap1) and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to enhance heme oxygenase-1 (HO-1) expression. In vivo, echinatin ameliorated LPS-induced lung inflammatory injury, and reduced production of IL-1β and IL-6. These findings demonstrated that echinatin exerted anti-inflammatory effects in vitro and in vivo, via blocking the TAK1-MAPK/NF-κB pathway and activating the Keap1-Nrf2-HO-1 pathway.

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Section: Resultsmentioning

confidence: 99%

Echinatin attenuates acute lung injury and inflammatory responses via TAK1-MAPK/NF-κB and Keap1-Nrf2-HO-1 signaling pathways in macrophages

Luo,

Wang,

Xiong

et al. 2024

PLoS ONE

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“…The characteristics of ferroptosis are consistent with several hallmarks of periodontitis pathogenesis [ 46 ]. For example, MDA, a by-product of lipid peroxidation and a marker of ferroptosis, has been reported in periodontium from patients with periodontitis [ 13 ] and in periodontal tissue, polyunsaturated fatty acids (PUFAs) increase and undergo a series of peroxidation reactions driven by LOX [ 47 ]. Ferroptosis is involved in inflammatory processes in HGFs upon P.g -LPS stimulation and observed in the gingival tissue of periodontitis rats [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Curcumin Attenuates Periodontal Injury via Inhibiting Ferroptosis of Ligature-Induced Periodontitis in Mice

Wang

Lin

Huang

et al. 2023

IJMS

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Periodontitis is a chronic infectious disease characterized by the destruction of connective tissue and alveolar bone that eventually leads to tooth loss. Ferroptosis is an iron-dependent regulated cell death and is involved in ligature-induced periodontitis in vivo. Studies have demonstrated that curcumin has a potential therapeutic effect on periodontitis, but the mechanism is still unclear. The purpose of this study was to investigate the protective effects of curcumin on alleviating ferroptosis in periodontitis. Ligature-induced periodontal-diseased mice were used to detect the protective effect of curcumin. The level of superoxide dismutase (SOD), malondialdehyde (MDA) and total glutathione (GSH) in gingiva and alveolar bone were assayed. Furthermore, the mRNA expression levels of acsl4, slc7a11, gpx4 and tfr1 were measured using qPCR and the protein expression of ACSL4, SLC7A11, GPX4 and TfR1 were investigated by Western blot and immunocytochemistry (IHC). Curcumin reduced the level of MDA and increased the level of GSH. Additionally, curcumin was proven to significantly increase the expression levels of SLC7A11 and GPX4 and inhibit the expression of ACSL4 and TfR1. In conclusion, curcumin plays a protective role by inhibiting ferroptosis in ligature-induced periodontal-diseased mice.

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“…We showed that ADSCs-Exos could reverse HG-induced Nrf2 reduction in vitro and in vivo, indicating that ADSCs-Exo can regulate high glucose-induced HO-1 dependent anti-inflammatory and anti-oxidative function in podocytes, which is related to the up-regulation of Nrf2 expression. Nrf2 binds to Keap1 under physiological conditions, resulting in increased ubiquitination on Nrf2 and promoting Nrf2 degradation through the ubiquitin-proteasome pathway [ 47 , 48 ]. Under oxidative stress, Nrf2 was transported to the nucleus and involved in the transcription of a series of antioxidant genes [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Adipose-derived stem cell exosomes regulate Nrf2/Keap1 in diabetic nephropathy by targeting FAM129B

Ren

Qian

et al. 2023

Diabetol Metab Syndr

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Background Exosomes from adipose-derived stem cells (ADSCs-Exos) have exhibited a therapeutic role in diabetic nephropathy (DN). Further studies are needed to investigate how ADSCs-Exos regulate oxidative stress and inflammation in high glucose-induced podocyte injury. Methods An enzyme-linked immunosorbent assay (ELISA) was used to detect cellular inflammation. Reactive oxygen species (ROS) levels were assessed using flow cytometry in podocytes with different treatments. A malondialdehyde (MDA) kit was used to evaluate the lipid peroxidation levels in podocytes and kidney tissues of mice. Western blotting and co-immunoprecipitation were performed to detect protein expression and protein-protein interactions. Results ADSCs-Exos reversed oxidative stress and inflammation in podocytes and kidney tissues of DN mice induced by high glucose levels in vitro and in vivo. Interference with heme oxygenase-1 expression could reverse the improvement effect of ADSCs-Exos on oxidative stress induced by high glucose levels. Furthermore, high glucose inhibited nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression and promoted Kelch-like ECH-associated protein 1 (Keap1) protein expression in podocytes, as well as their binding ability. As a potential target for Nrf2/Keap1 pathway regulation, FAM129B expression in podocytes is regulated by high glucose and ADSCs-Exos. Moreover, FAM129B siRNA blocked the inhibitory effect of ADSCs-Exos on intracellular ROS and MDA upregulation induced by high glucose in podocytes. Conclusion ADSCs-Exos regulate the Nrf2/Keap1 pathway to alleviate inflammation and oxidative stress in DN by targeting FAM129B, which may provide a potential therapeutic strategy for DN.

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The role of Nrf2 in periodontal disease by regulating lipid peroxidation, inflammation and apoptosis

Cited by 19 publications

References 121 publications

Echinatin attenuates acute lung injury and inflammatory responses via TAK1-MAPK/NF-κB and Keap1-Nrf2-HO-1 signaling pathways in macrophages

Echinatin attenuates acute lung injury and inflammatory responses via TAK1-MAPK/NF-κB and Keap1-Nrf2-HO-1 signaling pathways in macrophages

Curcumin Attenuates Periodontal Injury via Inhibiting Ferroptosis of Ligature-Induced Periodontitis in Mice

Adipose-derived stem cell exosomes regulate Nrf2/Keap1 in diabetic nephropathy by targeting FAM129B

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