METTL3 Regulates Liver Homeostasis, Hepatocyte Ploidy, and Circadian Rhythm–Controlled Gene Expression in Mice

Barajas, Juan M.; Lin, Cho-Hao; Sun, Hui-Lung; Alencastro, Frances; Zhu, Allen; Aljuhani, Mona; Navari, Ladan; Yilmaz, Selen; Yu, Lianbo; Corps, Kara N.; He, Chuan; Duncan, Andrew W.; Ghoshal, Kalpana

doi:10.1016/j.ajpath.2021.09.005

Cited by 28 publications

(8 citation statements)

References 64 publications

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“…First, CRD contributes directly to liver inflammation. As reported, the expressions of Mettl3, HDAC3, and Rev-erbα in the liver are affected by circadian rhythms. , CRD disrupts the expression of these genes, leading to hepatic immune dysregulation and exacerbating the development of liver diseases such as fatty liver, hepatitis, and hepatocellular carcinoma. , Second, the hepatic-intestinal cycle promoted the transmission of inflammation. It has been reported that CD4+ T helper cells (Th17) and macrophages in the intestine have circadian rhythm. , The dysregulation of CRD and gut microbes disrupts the immune cell rhythm, particularly Th17 and M1 macrophages, resulting in increased production of inflammatory factors such as IL-1β and IL-17. , Inflammatory factors enter the liver through the hepatic-intestinal circulation and increase inflammatory stress in the liver.…”

Section: Discussionmentioning

confidence: 82%

“…As reported, the expressions of Mettl3, HDAC3, and Rev-erbα in the liver are affected by circadian rhythms. 35,36 CRD disrupts the expression of these genes, leading to hepatic immune dysregulation and exacerbating the development of liver diseases such as fatty liver, hepatitis, and hepatocellular carcinoma. 37,38 Second, the hepatic-intestinal cycle promoted the transmission of inflammation.…”

Section: ■ Discussionmentioning

confidence: 99%

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Pu-erh Tea Restored Circadian Rhythm Disruption by Regulating Tryptophan Metabolism

Luo

Bian

et al. 2022

J. Agric. Food Chem.

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Pu-erh tea is a healthy beverage rich in phytochemicals, and its effect on the risk of inducing circadian rhythm disorders (CRD) is unclear. In this study, healthy mice were given water or 0.25% (w/v) Pu-erh tea for 7 weeks, followed by a 40 day disruption of the light/dark cycle. CRD caused dysregulation of neurotransmitter secretion and clock gene oscillations, intestinal inflammation, and disruption of intestinal microbes and metabolites. Pu-erh tea boosted the indole and 5-hydroxytryptamine pathways of tryptophan metabolism via the gut–liver–brain axis. Furthermore, its metabolites (e.g., IAA, Indole, 5-HT) enhanced hepatic glycolipid metabolism and down-regulated intestinal oxidative stress by improving the brain hormone release. Tryptophan metabolites and bile acids also promoted liver lipid metabolism and inhibited intestinal inflammation (MyD88/NF-κB) via the enterohepatic circulation. Collectively, 0.25% (w/v) Pu-erh tea has the potential to prevent CRD by promoting indole and 5-HT pathways of tryptophan metabolism and signaling interactions in the gut–liver–brain axis.

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Section: Discussionmentioning

confidence: 82%

Section: ■ Discussionmentioning

confidence: 99%

Pu-erh Tea Restored Circadian Rhythm Disruption by Regulating Tryptophan Metabolism

Luo

Bian

et al. 2022

J. Agric. Food Chem.

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“…IGF2BP2 raised EP300 to increase histone acetylation by binding LncRNA‐PACERR and interacting with intracellular KLF12, 36 and Hu et al 37 confirmed that EP300 was essential for the activity and stability of RUNX2 and the reduction of EP300 could inhibit osteoblast differentiation. Significant reductions in total BMAL1 and CLOCK mRNAs were observed after METTL3 knockout in mouse liver, 38 while Tang et al 39 revealed that upregulation of CLOCK/BMAL1 expression in osteoblasts could promote osteogenic differentiation. METTL3‐mediated m6A methylation modification in the 3′UTR of BMI1 mRNA, 40 while loss of IGF2BP2 led to the decay of Bmi1 mRNA 41 .…”

Section: Discussionmentioning

confidence: 99%

Changes in N6‐methyladenosine RNA methylomes of human periodontal ligament cells in response to inflammatory conditions

Zou

Liu

et al. 2023

J of Periodontal Research

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Objective To investigate the changes in the m6A methylation modification profile of human periodontal ligament cells (hPDLCs) in response to inflammatory conditions. Background Periodontitis is an infectious disease of the periodontal support tissue that leads to the loss of alveolar bone. HPDLCs are primary cells that can repair periodontal tissue defects caused by periodontitis. However, the inflammatory conditions induce inflammatory damage and decrease ossification of hPDLCs. This inflammatory response depends on genetic and epigenetic mechanisms, including m6A methylation. Methods HPDLCs were cultured with osteogenic induction medium (NC group), while TNF‐α (10 ng/mL) and IL‐1β (5 ng/mL) were added to simulate inflammatory conditions (Inflam group). Then RNA‐seq and MeRIP‐seq analyses were performed to identify m6A methylation modification in the transcriptome range of hPDLCs. Results The results showed that the osteogenic differentiation of hPDLCs was inhibited under inflammatory conditions. RNA‐seq analysis also revealed that the decreased genes in response to inflammatory conditions were primarily annotated in processes associated with ossification. Compared with the NC group, differentially m6A‐methylated genes were primarily enriched in histone modification processes. Among 145 histone modification genes, 25 genes have been reported to be involved in the regulation of osteogenic differentiation, and they include KAT6B, EP300, BMI1, and KDMs (KDM1A, KDM2A, KDM3A, KDM4B, and KDM5A). Conclusion This study demonstrated that the m6A landscape of hPDLCs was changed in response to inflammation. M6A methylation differences among histone modification genes may act on the osteogenic differentiation of hPDLCs.

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“…How their transcription is regulated in liver diseases needs further study. Recent studies show that m 6 A mRNA modification plays an important role in liver function, and hepatic deficiency of METTL3 (m 6 A methyltransferase) causes liver dysfunction and promotes NASH progression [94,95]. Interestingly, NIK has been shown to negatively regulate METTL3 expression [96].…”

Section: Future Perspectivesmentioning

confidence: 99%

Progress and Prospects of Non-Canonical NF-κB Signaling Pathway in the Regulation of Liver Diseases

Ren

Zhai

et al. 2022

Molecules

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Non-canonical nuclear factor kappa B (NF-κB) signaling pathway regulates many physiological and pathological processes, including liver homeostasis and diseases. Recent studies demonstrate that non-canonical NF-κB signaling pathway plays an essential role in hyperglycemia, non-alcoholic fatty liver disease, alcoholic liver disease, liver regeneration, liver injury, autoimmune liver disease, viral hepatitis, and hepatocellular carcinoma. Small-molecule inhibitors targeting to non-canonical NF-κB signaling pathway have been developed and shown promising results in the treatment of liver injuries. Here, the recent advances and future prospects in understanding the roles of the non-canonical NF-κB signaling pathways in the regulation of liver diseases are discussed.

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METTL3 Regulates Liver Homeostasis, Hepatocyte Ploidy, and Circadian Rhythm–Controlled Gene Expression in Mice

Cited by 28 publications

References 64 publications

Pu-erh Tea Restored Circadian Rhythm Disruption by Regulating Tryptophan Metabolism

Pu-erh Tea Restored Circadian Rhythm Disruption by Regulating Tryptophan Metabolism

Changes in N6‐methyladenosine RNA methylomes of human periodontal ligament cells in response to inflammatory conditions

Progress and Prospects of Non-Canonical NF-κB Signaling Pathway in the Regulation of Liver Diseases

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