Melatonin-induced lncRNA LINC01512 prevents Treg/Th17 imbalance by promoting SIRT1 expression in necrotizing enterocolitis

Gao, Xiaoyan; Liu, Wangkai; Gao, Pingming; Li, Sitao; Chen, Zhaoyu; Ma, Fei

doi:10.1016/j.intimp.2021.107787

Cited by 17 publications

(11 citation statements)

References 34 publications

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“…Necrotizing enterocolitis (NEC) is a severe inflammatory bowel necrosis that occurs mainly in premature infants. The imbalance of Th17/Treg is increasingly associated with NEC ( Gao et al, 2021 ). The lncRNA LINC01512 is downregulated in NEC patients, while melatonin upregulates LINC01512 through adenosine monophosphate-activated protein kinase (AMPK) signaling and interacts with sirtiun 1 (SIRT1), a regulator of various cellular and bodily processes.…”

Section: Lncrnas Modulate the Treg/th17 Balancementioning

confidence: 99%

“…The lncRNA LINC01512 is downregulated in NEC patients, while melatonin upregulates LINC01512 through adenosine monophosphate-activated protein kinase (AMPK) signaling and interacts with sirtiun 1 (SIRT1), a regulator of various cellular and bodily processes. Furthermore, LINC01512 promotes Treg differentiation and inhibits Th17 differentiation by enhancing SIRT1 expression, thereby administering to correct the imbalance of Treg/Th17 ratio ( Gao et al, 2021 ). The above melatonin-induced pathway may be a novel way to suppress inflammation.…”

Section: Lncrnas Modulate the Treg/th17 Balancementioning

confidence: 99%

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Long Noncoding RNAs as Orchestrators of CD4+ T-Cell Fate

Liu

Ma²,

Yi³

2022

Front. Cell Dev. Biol.

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CD4+ T cells differentiate towards different subpopulations through the regulation of lineage-specific cytokines and transcription factors, which flexibly respond to various immune challenges. However, considerable work has demonstrated that the CD4+ T-cell differentiation mechanism is complex and not limited to transcription factors and cytokines. Long noncoding RNAs (lncRNAs) are RNA molecules with lengths exceeding 200 base pairs that regulate various biological processes and genes. LncRNAs have been found to conciliate the plasticity of CD4+ T-cell differentiation. Then, we focused on lncRNAs involved in CD4+ T-cell differentiation and enlisted some molecular thought into the plasticity and functional heterogeneity of CD4+ T cells. Furthermore, elucidating how lncRNAs modulate CD4+ T-cell differentiation in disparate immune diseases may provide a basis for the pathological mechanism of immune-mediated diseases.

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Section: Lncrnas Modulate the Treg/th17 Balancementioning

confidence: 99%

Section: Lncrnas Modulate the Treg/th17 Balancementioning

confidence: 99%

Long Noncoding RNAs as Orchestrators of CD4+ T-Cell Fate

Liu

Ma²,

Yi³

2022

Front. Cell Dev. Biol.

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“…As a cocktail, EPO and MLT may additively and/or synergistically drive pathways to augment sustained neuro-immunomodulation and promote microenvironmental homeostasis. Notably, levels of the nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase sirtuin 1 (silent mating-type information regulation 2 homolog 1 [SIR], SIRT1) are elevated by both EPO [75,76] and MLT [77][78][79] (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

Infantile Cocktail of Erythropoietin and Melatonin Restores Gait in Adult Rats with Preterm Brain Injury

et al. 2022

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Cerebral palsy (CP) is the most common cause of physical disability for children worldwide. Many infants and toddlers are not diagnosed with CP until they fail to achieve obvious motor milestones. Currently, there are no effective pharmacologic interventions available for infants and toddlers to substantially improve their trajectory of neurodevelopment. Because children with CP from preterm birth also exhibit a sustained immune system hyper-reactivity, we hypothesized that neuro-immunomodulation with a regimen of repurposed endogenous neurorestorative medications, erythropoietin (EPO) and melatonin (MLT) could improve this trajectory. Thus, we administered EPO+MLT to rats with CP during human infant-toddler equivalency to determine whether we could influence gait patterns in mature animals. After a prenatal injury on embryonic day 18 (E18) that mimics chorioamnionitis at ~25 weeks human gestation, rat pups were born and raised with their dam. Beginning on postnatal day 15 (P15), equivalent to human infant ~1 year, rats were randomized to receive either a regimen of EPO+MLT or vehicle (sterile saline) through P20. Gait was assessed in young adult rats at P30 using computerized digital gait analyses including videography on a treadmill. Results indicate that gait metrics of young adult rats treated with an infantile cocktail of EPO+MLT were restored compared to vehicle-treated rats (p<0.05), and similar to sham controls. These results provide reassuring evidence that pharmacological interventions may be beneficial to infants and toddlers who are diagnosed with CP well after the traditional neonatal window of intervention.

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“…Immune dysregulation in NEC is caused based on elevated Th17 and reduced Treg cell activity, and there is a significant positive correlation between Th17/Treg cell ratio and NEC severity [ 37 ]. With the development of NEC, the attention on Th17 cells continues to increase, as well as serum IL-17 levels and cytokine levels associated with Th17 cell differentiation [ 38 ]. At the same time, the proportion of Treg cells in the body decreases, resulting in the inability to exert a highly potent immunosuppressive function and ultimately causing intestinal mucosal injury to induce NEC [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Sulforaphane Ameliorates the Intestinal Injury in Necrotizing Enterocolitis by Regulating the PI3K/Akt/GSK-3β Signaling Pathway

Bao

Xiong

et al. 2022

Canadian Journal of Gastroenterology and Hepatology

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Objective. Necrotizing enterocolitis (NEC) is a serious neonatal disease; this study aims to investigate the role of sulforaphane (SFN) in NEC-induced intestinal injury. Methods. An animal model of NEC was established in newborn mice and intragastrically administrated with SFN; then, the general status and survival of the mice were observed. H&E staining was used to observe the pathological changes of intestinal tissues. ELISA, immunohistochemical staining, and flow cytometry assays were used to detect the levels of inflammatory factors, including TNF-α, IL-6, and IL-17, the expression of Bax, Bcl-2, TLR4, and NF-κB, and the percentages of the Th17 and Treg cells, respectively. GSK-3β expression levels were measured by immunofluorescence. IEC-6 and FHC cells were induced with LPS to mimic NEC in vitro and coincubated with SFN; then, the inflammatory factor levels and cell apoptosis rate were detected. Finally, Western blot was used to assess the expression of PI3K/Akt/GSK-3β pathway-related proteins in vitro and in vivo. Results. SFN improved the survival rate of NEC mice during modeling, alleviated the severity of the intestinal injury, and reduced the proportion of Th17/Treg cells. SFN could inhibit TLR4 and NF-κB levels, decrease the release of inflammatory factors TNF-α and IL-6, suppress Bax expression, increase Bcl-2 expression, and inhibit apoptosis both in in vitro and in vivo models of NEC. Meanwhile, SFN regulated the expression of PI3K/Akt/GSK-3β pathway-related proteins in vitro and in vivo. Conclusion. SFN relieved the inflammatory response and apoptosis by regulating the PI3K/Akt/GSK-3β signaling pathway, thereby alleviating NEC in model mice and cells.

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Melatonin-induced lncRNA LINC01512 prevents Treg/Th17 imbalance by promoting SIRT1 expression in necrotizing enterocolitis

Cited by 17 publications

References 34 publications

Long Noncoding RNAs as Orchestrators of CD4+ T-Cell Fate

Long Noncoding RNAs as Orchestrators of CD4+ T-Cell Fate

Infantile Cocktail of Erythropoietin and Melatonin Restores Gait in Adult Rats with Preterm Brain Injury

Sulforaphane Ameliorates the Intestinal Injury in Necrotizing Enterocolitis by Regulating the PI3K/Akt/GSK-3β Signaling Pathway

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