Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity
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PROVIDER: PRJNA734601 | ENA |
REPOSITORIES: ENA
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Project description:Although the global prevalence of type 2 diabetes is still rising, the molecular mechanisms of dysregulated glucose and lipid metabolism are still incompletely understood. Epigenetic mechanisms were shown to have an impact in disease manifestation, but still the hepatic miRNA expression signature in diabetic subjects was not completely elucidated. We used microarrays to performe a genome wide screen of the complete noncoding RNA transcriptome in order to identify dsyregulated miRNAs which target genes of the hepatic glucose and lipid metabolism.
2023-10-31 | GSE176025 | GEO
Project description:A unique feature of the liver is its high regenerative capacity, which is essential to maintain liver homeostasis. However, key regulators of liver regeneration (LR) remain ill-defined. Here, we identify hepatic miR-182-5p as a key regulator of LR. Suppressing miR-182-5p, whose expression is significantly induced in the liver of mice post two-thirds partial hepatectomy (PH), abrogates PH-induced LR in mice. In contrast, liver-specific overexpression of miR-182-5p promotes LR in mice with PH. Overexpression of miR-182-5p failed to promote proliferation in hepatocytes, but stimulates proliferation when hepatocytes are cocultured with stellate cells. Mechanistically, miR-182-5p stimulates Cyp7a1-mediated cholic acid production in hepatocytes, which promotes hedgehog (Hh) ligand production in stellate cells, leading to the activation of Hh signaling in hepatocytes and consequent cell proliferation. Collectively, our study identified miR-182-5p as a critical regulator of LR and uncovers a Cyp7a1/cholic acid-dependent mechanism by which hepatocytes crosstalk to stellate cells to facilitate LR.
2022-08-10 | GSE206451 | GEO
Project description:Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with NAFLD and its progression. Microarrays were used to identify hepatic gene expression changes in each of these models. The goal is to identify a predictor of different NAFLD progressions. Non-alcoholic fatty liver disease (NAFLD) is recognized as a low-grade systemic inflammatory state with both hepatic and extra-hepatic manifestations. We aimed to identify common key regulators and adaptive pathways in different NAFLD phenotypes. NAFL, NASH and NAFL+T2DM rat models were used to represent simple fatty liver, fatty liver with severe hepatic manifestations, and fatty liver with severe metabolic manifestations, respectively. We applied microarray analysis to characterize the key regulators and adaptive pathways in different NAFLD phenotypes. There are 12 samples in our study which belonged to 4 groups, and each group contains 3 different samples.
2015-01-23 | E-GEOD-65220 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with NAFLD and its progression. Microarrays were used to identify hepatic gene expression changes in each of these models. The goal is to identify a predictor of different NAFLD progressions. Non-alcoholic fatty liver disease (NAFLD) is recognized as a low-grade systemic inflammatory state with both hepatic and extra-hepatic manifestations. We aimed to identify common key regulators and adaptive pathways in different NAFLD phenotypes. NAFL, NASH and NAFL+T2DM rat models were used to represent simple fatty liver, fatty liver with severe hepatic manifestations, and fatty liver with severe metabolic manifestations, respectively. We applied microarray analysis to characterize the key regulators and adaptive pathways in different NAFLD phenotypes.
2015-01-23 | GSE65220 | GEO
Project description:To identify genes differentially modulated by anti-miR-182 treatment in a liver melanoma metastasis mouse model. Targeting oncogenic microRNAs is emerging as a promising strategy for cancer therapy. Here we provide proof-of-principle for the safety and efficacy of miRNA targeting against metastatic tumors. We tested the effect of targeting miR-182, a pro-metastatic miRNA frequently overexpressed in melanoma, whose silencing represses invasion and induces apoptosis in vitro. In particular, we assessed the effect of anti-miR-182 oligonucleotides synthesized with 2’ sugar modifications and a phosphorothioate backbone in a mouse model of melanoma liver metastasis. Luciferase imaging showed that mice treated with anti-miR-182 had an appreciably lower burden of liver metastases compared to the control. We confirmed that miR-182 levels were effectively downregulated in the anti-miR treated tumors relative to the scrambled treated tumor both in the liver and in the spleen. This downregulation was accompanied by an upregulation of miR-182 direct targets. Transcriptome analysis of mouse tissues treated with anti-miR-182 or scramble oligonucleotides revealed an enrichment for genes controlling survival, adhesion and migration modulated in response to anti-miR-182 treatment. These data indicate that in vivo administration of anti-miRs allows for efficient miRNA targeting and concomitant upregulation of target levels. Our results suggest that the use of anti-miR-182 is a promising therapeutic strategy for metastatic melanoma and provide solid proof-of-principle for similar strategies against other metastatic tumors. Keywords: Differentially expressed genes (mRNAs) in response to miRNA inhibition
2010-10-21 | GSE24824 | GEO
Project description:To identify genes differentially modulated by anti-miR-182 treatment in a liver melanoma metastasis mouse model. Targeting oncogenic microRNAs is emerging as a promising strategy for cancer therapy. Here we provide proof-of-principle for the safety and efficacy of miRNA targeting against metastatic tumors. We tested the effect of targeting miR-182, a pro-metastatic miRNA frequently overexpressed in melanoma, whose silencing represses invasion and induces apoptosis in vitro. In particular, we assessed the effect of anti-miR-182 oligonucleotides synthesized with 2â sugar modifications and a phosphorothioate backbone in a mouse model of melanoma liver metastasis. Luciferase imaging showed that mice treated with anti-miR-182 had an appreciably lower burden of liver metastases compared to the control. We confirmed that miR-182 levels were effectively downregulated in the anti-miR treated tumors relative to the scrambled treated tumor both in the liver and in the spleen. This downregulation was accompanied by an upregulation of miR-182 direct targets. Transcriptome analysis of mouse tissues treated with anti-miR-182 or scramble oligonucleotides revealed an enrichment for genes controlling survival, adhesion and migration modulated in response to anti-miR-182 treatment. These data indicate that in vivo administration of anti-miRs allows for efficient miRNA targeting and concomitant upregulation of target levels. Our results suggest that the use of anti-miR-182 is a promising therapeutic strategy for metastatic melanoma and provide solid proof-of-principle for similar strategies against other metastatic tumors. Keywords: Differentially expressed genes (mRNAs) in response to miRNA inhibition Quadruplicate (n=4) samples of anti-miR-182 treated human melanoma metastasis compared to quadruplicate control treated metastasis.
2010-10-21 | E-GEOD-24824 | biostudies-arrayexpress
Project description:Kupffer cells (KCs) are tissue-resident macrophages which colonize the liver early during embryogenesis. KCs start to acquire a tissue-specific transcriptional signature immediately after colonizing the liver, mature together with the tissue, and adapt to the tissue’s functions. Throughout development and adulthood, KCs have distinct core functions that are essential for liver and organismal homeostasis, such as supporting fetal erythropoiesis as well as postnatal erythrocyte recycling and liver metabolism. However, whether perturbations of macrophage core functions during development contribute to or cause disease at postnatal stages is poorly understood. Here, we utilize a mouse model of maternal obesity to perturb KC functions during gestation. We show that offspring exposed to maternal obesity develop fatty liver disease, driven by aberrant developmental programming of KCs that persists into adulthood. Programmed KCs mediate lipid uptake by hepatocytes through apolipoprotein secretion. KC depletion in neonates born to obese mothers, followed by replenishment with exogenous monocytes, rescues the fatty liver disease. The transcriptional programming of KCs and the fatty liver disease phenotype are also rescued by genetic depletion of hypoxia-inducible factor alpha (Hif1a) in macrophages during gestation. These results establish developmental perturbation of KC functions as a cause for the development of fatty liver disease in adult life and, thereby, place fetal-derived macrophages as intergenerational messengers within the concept of developmental origins of health and diseases.
2024-12-04 | GSE283082 | GEO
Project description:Immunosenescence and exhaustion are involved in the development and progression of type 2 diabetes (T2D) and metabolic liver diseases, including fatty liver, fibrosis, and cirrhosis, in humans. However, the relationships of the senescence and exhaustion of T cells with insulin resistance-associated liver diseases remain incompletely understood. To better define the relationship of T2D with nonalcoholic fatty liver disease, 59 patients with T2D were studied.
2023-08-05 | GSE239612 | GEO
Project description:Hepatocyte mARC1 Promotes Fatty Liver Disease
| PRJNA927038 | ENA