Activation of Autophagy Through the NLRP3/mTOR Pathway: A Potential Mechanism for Alleviation of Pneumonia by QingFei Yin

Sun, Xiaozhou; Wang, Dandan; Ding, Lizhong; Xu, Yan; Qi, Wenxiu; Zhao, Daqing; Liu, Li; Yin, Chengcheng; Cui, Changsheng; Wang, Zhongtian; Sun, Liwei; Li-ping, Sun

doi:10.3389/fphar.2021.763160

Cited by 4 publications

(3 citation statements)

References 55 publications

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“…45 The protein level of the NLRP3 pathway is potentially associated with p-mTOR/mTOR. 46 More directly, it has been revealed that NLRP3 and mTOR can bind directly and play a regulatory role in innate immunity. 41,46−48 In this study, we observed that the phosphorylation of mTOR was inhibited by FB 1 treatment.…”

Section: Discussionmentioning

confidence: 99%

mTOR-Mediated Autophagy Regulates Fumonisin B₁-Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro

Liu

et al. 2022

J. Agric. Food Chem.

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Fumonisin B 1 (FB 1 ) is a fungal metabolite, which has an incremental detection rate in grains and feed worldwide. The nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) inflammasome is a critical element in pyroptosis activation, which participates in regulating enteritis. Meanwhile, autophagy is also engaged in intestinal inflammation. However, the function of pyroptosis and autophagy in FB 1 -mediated enterotoxicity remains unclear. In this study, we explored the effects of FB 1 on enteritis and the underlying mechanism in vivo and in vitro. Our data showed that FB 1 exposure damaged the intestinal epithelium and promoted the secretion of inflammatory cytokines. Meanwhile, FB 1 exposure significantly upregulated the expression of pyroptosis-related genes. Then, MCC950, an inhibitor of NLRP3, significantly blocked FB 1 -induced pyroptosis in IPEC-J2 cells. In addition, FB 1 treatment elevated the levels of autophagy. Moreover, the phosphorylation of the mammalian target of rapamycin (mTOR), an upstream protein of the autophagy pathway, was inhibited by FB 1 exposure. Notably, rapamycin, an inhibitor of mTOR, instead of MHY1485, an agonist of mTOR, could ameliorate FB 1 -induced intestinal inflammatory injury and inhibit the upregulation of pyroptosis-related genes. In summary, we demonstrated that autophagy exhibited a protective effect against NLRP3 inflammasome-dependent pyroptosis on FB 1 -induced enteritis. Our data clarify a favorable protective role for the activation of autophagy in FB 1 poisoning.

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Section: Discussionmentioning

confidence: 99%

mTOR-Mediated Autophagy Regulates Fumonisin B₁-Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro

Liu

et al. 2022

J. Agric. Food Chem.

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“…Autophagy is a self-degrading process that promotes cellular survival responses to nutrient starvation or stress conditions by removing damaged proteins and organelles (Xie et al, 2014). Excessive autophagy can degrade normal protein and organelle functions in tumor cells, destroy cells, and even cause programmed cell death in non-apoptotic pathways (Sun et al, 2022). The formation of autophagosomes is a hallmark of autophagy (Zhang L et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Salvia chinensia Benth induces autophagy in esophageal cancer cells via AMPK/ULK1 signaling pathway

et al. 2022

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Salvia chinensia Benth (Shijianchuan in Chinese, SJC) has been used as a traditional anti-cancer herb. SJC showed good anti-esophageal cancer efficacy based on our clinical application. However, the current research on SJC is minimal, and its anti-cancer effect lacks scientific certification. This study aims to clarify the inhibitory effect of SJC on esophageal cancer and explore its underlying mechanism. Q-Orbitrap high-resolution LC/MS was used to identify the primary chemical constituents in SJC. Cell proliferation and colony formation assays showed that SJC could effectively inhibit the growth of esophageal tumor cells in vitro. To clarify its mechanism of action, proteomic and bioinformatic analyses were carried out by combining tandem mass labeling and two-dimensional liquid chromatography-mass spectrometry (LC-MS). Data are available via ProteomeXchange with identifier PXD035823. The results indicated that SJC could activate AMPK signaling pathway and effectively promote autophagy in esophageal cancer cells. Therefore, we further used western blotting to confirm that SJC activated autophagy in esophageal cancer cells through the AMPK/ULK1 signaling pathway. The results showed that P-AMPK and P-ULK1 were significantly up-regulated after the treatment with SJC. The ratio of autophagosomes marker proteins LC3II/I was significantly increased. In addition, the expression of the autophagy substrate protein P62 decreased with the degradation of autophagosomes. Using lentiviral transfection of fluorescent label SensGFP-StubRFP-LC3 protein and revalidation of LC3 expression before and after administration by laser confocal microscopy. Compared with the control group, the fluorescence expression of the SJC group was significantly enhanced, indicating that it promoted autophagy in esophageal cancer cells. Cell morphology and the formation of autophagosomes were observed by transmission electron microscopy. Our study shows that the tumor suppressor effect of SJC is related to promoting autophagy in esophageal tumor cells via the AMPK/ULK1 signaling pathway.

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“…The X‐ray system of the scanner used a micro‐focus X‐ray tube, which scanned various levels of the coccyx using a cone‐shaped beam under the condition of 4 W power and a focal size of 5 μm. Imaging at different 360° angles was conducted using an X‐ray tube with 90 kVp and 160 μA, with a total scanning time of 14 min (Sun, Wang, Ding, et al., 2021; Sun, Wang, Wei, et al., 2021).…”

Section: Methodsmentioning

confidence: 99%

Regulatory mechanism of FCGR2A in macrophage polarization and its effects on intervertebral disc degeneration

Luo,

Jin,

Cui

et al. 2024

The Journal of Physiology

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Intervertebral disc degeneration (IDD) poses a significant health burden, necessitating a deeper understanding of its molecular underpinnings. Transcriptomic analysis reveals 485 differentially expressed genes (DEGs) associated with IDD, underscoring the importance of immune regulation. Weighted gene co‐expression network analysis (WGCNA) identifies a yellow module strongly correlated with IDD, intersecting with 197 DEGs. Protein–protein interaction (PPI) analysis identifies ITGAX, MMP9 and FCGR2A as hub genes, predominantly expressed in macrophages. Functional validation through in vitro and in vivo experiments demonstrates the pivotal role of FCGR2A in macrophage polarization and IDD progression. Mechanistically, FCGR2A knockdown suppresses M1 macrophage polarization and NF‐κB phosphorylation while enhancing M2 polarization and STAT3 activation, leading to ameliorated IDD in animal models. This study sheds light on the regulatory function of FCGR2A in macrophage polarization, offering novel insights for IDD intervention strategies. imageKey points This study unveils the role of FCGR2A in intervertebral disc (IVD) degeneration (IDD). FCGR2A knockdown mitigates IDD in cellular and animal models. Single‐cell RNA‐sequencing uncovers diverse macrophage subpopulations in degenerated IVDs. This study reveals the molecular mechanism of FCGR2A in regulating macrophage polarization. This study confirms the role of the NF‐κB/STAT3 pathway in regulating macrophage polarization in IDD.

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Activation of Autophagy Through the NLRP3/mTOR Pathway: A Potential Mechanism for Alleviation of Pneumonia by QingFei Yin

Cited by 4 publications

References 55 publications

mTOR-Mediated Autophagy Regulates Fumonisin B₁-Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro

mTOR-Mediated Autophagy Regulates Fumonisin B₁-Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro

Salvia chinensia Benth induces autophagy in esophageal cancer cells via AMPK/ULK1 signaling pathway

Regulatory mechanism of FCGR2A in macrophage polarization and its effects on intervertebral disc degeneration

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Activation of Autophagy Through the NLRP3/mTOR Pathway: A Potential Mechanism for Alleviation of Pneumonia by QingFei Yin

Cited by 4 publications

References 55 publications

mTOR-Mediated Autophagy Regulates Fumonisin B1-Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro

mTOR-Mediated Autophagy Regulates Fumonisin B1-Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro

Salvia chinensia Benth induces autophagy in esophageal cancer cells via AMPK/ULK1 signaling pathway

Regulatory mechanism of FCGR2A in macrophage polarization and its effects on intervertebral disc degeneration

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Product

Resources

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mTOR-Mediated Autophagy Regulates Fumonisin B₁-Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro

mTOR-Mediated Autophagy Regulates Fumonisin B₁-Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro