A Data-Mining Approach to Identify NF-kB-Responsive microRNAs in Tissues Involved in Inflammatory Processes: Potential Relevance in Age-Related Diseases

Micolucci, Luigina; Matacchione, Giulia; Albertini, Maria Cristina; Marra, Massimo; Ramini, Deborah; Giuliani, Angelica; Procopio, Antonio Domenico; Olivieri, Fabiola; Marsico, Annalisa; Monsurró, Vladia

doi:10.3390/ijms24065123

Cited by 3 publications

(1 citation statement)

References 135 publications

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“…One of the most well studied inducers of senescence in NP cells is TNFα [9,21], however the mechanism through which TNFα induces senescence is still not fully delineated. Studies have implicated PI3K-Akt [21], pSTAT3 [22], miRNAs [23], and SIRT [24] as potential signaling mechanisms. Recent work has demonstrated that TNFα induced senescent NP cells secrete soluble factors that are capable of inducing senescence in healthy NP cells [22], however the effect of these soluble factors on AF cells have not been assessed [25].…”

Section: Introductionmentioning

confidence: 99%

Senescent response in inner annulus fibrosus cells in response to TNFα, H2O2, and TNFα-induced nucleus pulposus senescent secretome

Montgomery-Song,

Ashraf,

Santerre

et al. 2024

PLoS ONE

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Senescence, particularly in the nucleus pulposus (NP) cells, has been implicated in the pathogenesis of disc degeneration, however, the mechanism(s) of annulus fibrosus (AF) cell senescence is still not well understood. Both TNFα and H2O2, have been implicated as contributors to the senescence pathways, and their levels are increased in degenerated discs when compared to healthy discs. Thus, the objective of this study is to identify factor(s) that induces inner AF (iAF) cell senescence. Under TNFα exposure, at a concentration previously shown to induce senescence in NP cells, bovine iAF cells did not undergo senescence, indicated by their ability to continue to proliferate as demonstrated by Ki67 staining and growth curves and lack of expression of the senescent markers, p16 and p21. The lack of senescent response occurred even though iAF express higher levels of TNFR1 than NP cells. Interestingly, iAF cells showed no increase in intracellular ROS or secreted H2O2 in response to TNFα which contrasted to NP cells that did. Following TNFα treatment, only iAF cells had increased expression of the superoxide scavengers SOD1 and SOD2 whereas NP cells had increased NOX4 gene expression, an enzyme that can generate H2O2. Treating iAF cells with low dose H2O2 (50 μM) induced senescence, however unlike TNFα, H2O2 did not induce degenerative-like changes as there was no difference in COL2, ACAN, MMP13, or IL6 gene expression or number of COL2 and ACAN immunopositive cells compared to untreated controls. The latter result suggests that iAF cells may have distinct degenerative and senescent phenotypes. To evaluate paracrine signalling by senescent NP cells, iAF and TNFα-treated NP cells were co-cultured. In contact co-culture the NP cells induced iAF senescence. Thus, senescent NP cells may secrete soluble factors that induce degenerative and senescent changes within the iAF. This may contribute to a positive feedback loop of disc degeneration. It is possible these factors may include H2O2 and cytokines (such as TNFα). Further studies will investigate if human disc cells respond similarly.

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Section: Introductionmentioning

confidence: 99%

Senescent response in inner annulus fibrosus cells in response to TNFα, H2O2, and TNFα-induced nucleus pulposus senescent secretome

Montgomery-Song,

Ashraf,

Santerre

et al. 2024

PLoS ONE

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Periodic protein‐restricted diets extend the lifespan of high‐fat diet‐induced Drosophila melanogaster males

Wang,

Zhu,

Huang

et al. 2024

Aging Cell

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Research has shown that sustained protein restriction can improve the effects of a high‐fat diet on health and extend lifespan. However, long‐term adherence to a protein‐restricted diet is challenging. Therefore, we used a fly model to investigate whether periodic protein restriction (PPR) could also mitigate the potential adverse effects of a high‐fat diet and extend healthy lifespan. Our study results showed that PPR reduced body weight, lipid levels, and oxidative stress induced by a high‐fat diet in flies and significantly extended the healthy lifespan of male flies. Lipid metabolism and transcriptome results revealed that the common differences between the PPR group and the control group and high‐fat group showed a significant decrease in palmitic acid in the PPR group; the enriched common differential pathways Toll and Imd were significantly inhibited in the PPR group. Further analysis indicated a significant positive correlation between palmitic acid levels and gene expression in the Toll and Imd pathways. This suggests that PPR effectively improves fruit fly lipid metabolism, reduces palmitic acid levels, and thereby suppresses the Toll and Imd pathways to extend the healthy lifespan of flies. Our study provides a theoretical basis for the long‐term effects of PPR on health and offers a new dietary adjustment option for maintaining health in the long term.

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miR-26a Improves Microglial Activation and Neuronal Apoptosis in a Rat Model of Cerebral Infarction by Regulating the TREM1-TLR4/MyD88/NF-κB Axis

Xu,

Guo

2023

Dev Neurosci

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Emerging studies have indicated that abnormally expressed microRNAs (miRNAs) are related to the pathogenesis of cerebral ischemia. Nevertheless, the function of miR-26a in neuronal damage and microglial activation during cerebral infarction remains elusive. It was revealed that miR-26a was downregulated in oxygen-glucose deprivation (OGD)-treated microglia and neurons. Overexpressing miR-26a reduced the inflammatory reaction in BV2 cells and decreased neuronal apoptosis following OGD stimulation. miR-26a upregulation inactivated the TLR4/MyD88/NF-κB pathway and inhibited TREM1 expression. Repressing NF-κB phosphorylation inhibited the miR-26a level. As supported by the dual-luciferase reporter assay, TREM1 was directly targeted by miR-26a. Furthermore, a rat model of middle cerebral artery occlusion (MCAO) was built. We discovered that miR-26a improved cognitive, learning and motor functions and reduced cerebral edema in MCAO rats. Mechanistically, upregulating miR-26a reduced inflammation and neuronal apoptosis by mitigating the TREM1-TLR4/MyD88/NF-κB pathway in the MCAO rat model. Collectively, this study verified that the miR-26a-TREM1-TLR4/MyD88/NF-κB axis contributes to modulating OGD-mediated microglial activation and neuronal injury.

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A Data-Mining Approach to Identify NF-kB-Responsive microRNAs in Tissues Involved in Inflammatory Processes: Potential Relevance in Age-Related Diseases

Cited by 3 publications

References 135 publications

Senescent response in inner annulus fibrosus cells in response to TNFα, H2O2, and TNFα-induced nucleus pulposus senescent secretome

Senescent response in inner annulus fibrosus cells in response to TNFα, H2O2, and TNFα-induced nucleus pulposus senescent secretome

Periodic protein‐restricted diets extend the lifespan of high‐fat diet‐induced Drosophila melanogaster males

miR-26a Improves Microglial Activation and Neuronal Apoptosis in a Rat Model of Cerebral Infarction by Regulating the TREM1-TLR4/MyD88/NF-κB Axis

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