Metformin on human macrophages
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ABSTRACT:
PROVIDER: PRJNA642127 | ENA |
REPOSITORIES: ENA
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Project description:Metformin on human macrophages Human blood derived macrophages were treated with 10micromolar Metformin (Sigma-Aldrich) for 4h
2020-06-27 | GSE153318 | GEO
Project description:Metformin is a front-line drug in the treatment of type-2 diabetes mellitus (T2DM). In addition to its antigluconeogenic and insulin-sensitizing properties, it has emerged as a potent inhibitor of the inflammatory response of macrophages. Specifically, metformin has been shown to reduce transcript levels of Il1b, the gene encoding the pro-inflammatory cytokine interleukin (IL)-1b, during long-term exposure of macrophages to the bacterial cell-wall component lipopolysaccharide (LPS). However, the extent to which metformin affects the early transcriptional response to LPS has never been investigated. Here, we show that metformin affects transcript levels of a large yet selective subset of LPS-responsive genes after only two hours of LPS exposure, mostly counteracting the effect of LPS rather than enhancing it. The affected genes are implicated in a variety of biological functions, in particular cellular movement and trafficking. Intriguingly, metformin affects transcript levels of Il1b at this early time point as well, but through a molecular mechanism fundamentally different from the regulation observed after longer exposure. While down-regulation of Il1b by metformin during the late stages of the LPS response has been shown to rely on stabilization of hypoxia-inducible factor (HIF)-1α and production of IL-10, Il1b inhibition at the early stage requires AMP-activated protein kinase (AMPK) activation but is independent of HIF-1α and IL-10. These results reveal an unexpected complexity in the anti-inflammatory properties of metformin and demonstrate that Il1b is down-regulated by distinct mechanisms in the early and late stages of the LPS response.
2021-08-30 | GSE131348 | GEO
Project description:To test the effects of metformin on the human gut micorbiome, we fist collected human stool samples. We processed the samples in vitro culturing under anaerobic condition for 24 hours using the rapidAIM assay and either and cultured them with metformin, or DMSO as a control. We know that metformin can alter the human gut microbiome and were interested in better analyzing which functional proceses were altered.
2021-03-16 | PXD016427 | Pride
Project description:Metformin rejuvenates adult rat oligodendrocyte progenitor cells (OPCs) allowing more efficient differentiation into oligodendrocytes and improved remyelination of CNS axons and therefore is of interest as a possible therapeutic in demyelinating diseases such as multiple sclerosis (MS). We set out to test whether metformin had a similar effect in human stem cell derived-OPCs. We assessed the suitability of human monoculture, organoid and transplantation into immunodeficient mice (chimera model) culture systems in simulating in vivo adult human oligodendrocytes, finding most close resemblance in the chimera model. Metformin increased myelin proteins and/or sheaths in all models even when human cells had fetal signatures. In the chimera model, metformin led to a marked increase in mitochondrial area both in the human transplanted cells and in the mouse axons with associated increase in transcripts related to mitochondrial function and metabolism. Human oligodendrocytes from MS brain donors treated pre-mortem with metformin also expressed similar transcripts suggesting that metformin’s brain effect is not cell-specific, altering metabolism in both oligodendrocytes and axons leading to more myelin production, in part through mitochondrial changes. This bodes well for ongoing clinical trials testing metformin for neuroprotection.
2024-12-10 | GSE282369 | GEO
Project description:The biguanide metformin has been shown to not only reduce circulating glucose levels but also suppress in vitro and in vivo growth of prostate cancer. However, the mechanisms underlying the anti-tumor effects of metformin in advanced prostate cancers are not fully understood. The goal of the present study was to define the signaling pathways regulated by metformin in androgen-receptor (AR) positive, castration-resistant prostate cancers. Our group used RNA sequencing (RNA-seq) to examine genes regulated by metformin within the C4-2 human prostate cancer cell line. Western blot analysis and quantitative RT-PCR were used to confirm alterations in gene expression and further explore regulation of protein expression by metformin. Data from the RNA-seq analysis revealed that metformin alters the expression of genes products involved in metabolic pathways, the spliceosome, RNA transport, and protein processing within the endoplasmic reticulum. Gene products involved in ErbB, insulin, mTOR, TGF-, MAPK, and Wnt signaling pathways are also regulated by metformin. A subset of metformin-regulated gene products were genes known to be direct transcriptional targets of p53 or AR. Together, our results suggest metformin regulates multiple pathways linked to tumor growth and progression within advanced prostate cancer cells.
2022-02-10 | GSE196343 | GEO
Project description:As our results suggested that metformin acts to limit mitochondrial ROS and calcium-mediated activation of IL-6, we reasoned it would likely affect other processes in alveolar macrophages triggered by exposure to particulate matter (PM). Therefore, we treated mice with metformin in the drinking water for 24 hours before we instilled PM intratracheally. We then flow-sorted alveolar macrophages from whole lung homogenates 24 hours later for transcriptomic analysis (RNA-Seq).
2018-10-05 | GSE98731 | GEO
Project description:Phase 1, first-in-human, open label study of CAR macrophages in HER2 overexpressing solid tumors.
| 2360169 | ecrin-mdr-crc
Project description:To examine the effect of metformin on lung cancer biology, human lung H226 and H1299 squamous cell carcinoma cell-lines were grown in RPMI-1640 medium with 10% v/v fetal bovine serum and with or without 15 uM metformin hydrochloride for 7-8 days. Medium (with any metformin) was replaced every two days. Paired cultures with and without metformin were grown and maintained in parallel. Three separate paired cultures, all seeded with same stock of frozen cells, were grown.
2020-02-29 | E-MTAB-8782 | biostudies-arrayexpress
Project description:Metformin restores myelination potential of aged rat A2B5+ oligodendroglia (OL) progenitor cells and may enhance recovery in children with post-radiation brain injury. Human late progenitor cells (O4+A2B5+) have superior capacity to ensheath nanofibers compared to mature OLs, with cells from pediatric sources exceeding adults. In this study we assessed effects of metformin on ensheathment capacity of human adult and pediatric progenitors and mature OLs and relate differences to transcriptional changes. A2B5+ progenitors and mature OLs, derived from surgical tissues by immune-magnetic separation, were assessed for ensheathment capacity in nanofiber plates over 2 weeks. Metformin (10µM every other day) was added to selected cultures. RNA was extracted from treated and control cultures after 2 days. For all ages, ensheathment by progenitors exceeded mature OLs. Metformin enhanced ensheathment by adult donor cells but reduced ensheathment by pediatric cells. Metformin marginally increased cell death in pediatric progenitors. Metformin induced changes in gene expression distinct for each cell type. Adult progenitors showed up-regulation of pathways involved in process outgrowth and promoting lipid biosynthesis. Pediatric progenitors showed a relatively greater proportion of down- versus up-regulated pathways, these involved cell morphology, development, and synaptic transmission. Metformin induced AMPK activation in all cell types; AMPK inhibitor BML-275 reduced functional metformin effects only with adult cells. Our results indicate age and differentiation stage related differences of human OL lineage cells in response to metformin. Clinical trials for demyelinating conditions will indicate how these differences translate in vivo.
2023-11-11 | GSE247159 | GEO
Project description:Inflammation, oxidative and dicarbonyl stress play important roles in the pathophysiology of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver, however, its “pleiotropic“ effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP). In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL6 while levels of human CRP remained unchanged and metformin also significantly reduced oxidative stress (levels of conjugated dienes and TBARS) in the liver while no significant effects were observed in SHR control rats. In addition, in the presence of high human CRP, metformin reduced methylglyoxal levels in left ventricles but not in kidneys. Finally, metformin treatment reduced adipose tissue lipolysis. Possible molecular mechanisms of metformin action studied by gene expression profiling in the liver revealed deregulated genes from inflammatory, insulin signaling, AMP-activated protein kinase (AMPK) signaling and gluconeogenesis pathways. It can be concluded that in the presence of high levels of human CRP metformin protects against inflammation, oxidative and dicarbonyl stress in the heart and ameliorates insulin resistance and dyslipidemia.
2016-07-03 | E-MTAB-3791 | biostudies-arrayexpress