Bulk RNA-seq of colonic epithelial stem cell-derived organoids from healthy epithelial HO-1 knockout and control mice exposed to hemin vs vehicle
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE312912 | GEO | 2025/12/12
REPOSITORIES: GEO
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Project description:Heme, an iron-containing prosthetic group found in many proteins, carries out diverse biological functions such as electron transfer, oxygen storage and enzymatic reactions. Hemin, the oxidised form of heme, is used to treat porphyria and also to activate heme-oxygenase (HO) which catalyses the rate-limiting step in heme degradation. Our group has previously demonstrated that hemin displays antitumor activity in breast cancer (BC). The aim of this work has been to study the effect of hemin on protein expression modifications in a BC cell line to gain insight into the molecular mechanisms of hemin antitumor activity. For this purpose, we carried out proteome analysis by Mass Spectrometry (MS) which showed that 1309 proteins were significantly increased in hemin-treated cells, including HO-1 and the proteases that regulate HO-1 function, and 921 proteins were significantly decreased. Furthermore, the MS-data analysis showed that hemin regulates the expression of heme- and iron- related proteins, adhesion and cytoskeletal proteins, cancer signal transduction proteins and enzymes involved in lipid metabolism. By biochemical and cellular studies, we further corroborated the most relevant in-silico results. Altogether, these results show the multiple physiological effects that hemin treatment displays in BC and demonstrate its potential as anticancer agent.
2023-07-20 | PXD036701 | Pride
Project description:Bulk RNA-seq of colonic epithelial stem cell-derived organoids from healthy epithelial HO-1 knockout and control mice exposed to hemin vs vehicle
| PRJNA1377590 | ENA
Project description:The aim was to determine the effect of heme oxygenase-1 (HO-1) overexpression on microRNA transcriptome in human non-small cell lung carcinoma cell line (NCI-H292). Since the cells of different HO-1 genotypes were used (cells are after retroviral transduction with empty vector with normal level of HO-1 or retroviral transduction with vector harboring HO-1), it is possible get the comprehensive answer which microRNAs are regulated by HO-1.
2013-04-27 | GSE37779 | GEO
Project description:Metabolic adaptation refers to the regulation of cellular metabolism to prevent tissue dysfunction in response to different forms of stress. Heme, an iron-containing porphyrin, is indispensable for oxygen transport and for the activity of hemoproteins such as catalases. Cytotoxic “labile” heme is readily degraded by two distinct heme oxygenases (HO). The conditional deletion of Hmox-1, the gene encoding the inducible heme-degrading enzyme heme oxygenase (HO)-1, impairs metabolic adaptation to malaria and to polymicrobial infection. Embryonic deficiency in HO-1 is partially lethal in mice and surviving animals show progressive chronic inflammatory disease making them an unsuitable model to study metabolic adaptation. Here we found that mice with an inducible deletion of Hmox1 (Hmox1R26Δ/Δ) but not control mice rapidly succumbed to sterile hemolytic stress. Mortality was associated with heme-driven kidney failure, hypoglycemia, and disruption of adaptive thermoregulation. RNA sequencing and targeted metabolomics combined with data-driven in silico metabolic modeling revealed that failed renal metabolic adaptation is driven by altered oxidative phosphorylation and impaired pentose phosphate pathway. Heme-induced kidney failure and mortality in Hmox1R26Δ/Δ mice was not prevented with impairment of the inflammatory response, nor with antioxidants. Our results emphasize the critical importance of Hmox1 expression in hemolytic stress leading to acute kidney injury and death.
2025-12-02 | GSE246570 | GEO
Project description:Many phytopathogens such as Ustilago maydis rely on their hosts for nutrients during disease. In this study, we tried to identify key genes involved in heme uptake and gain a deeper understanding of the transcriptional response to hemin treatment. We observed upregulations in ergosterol biosynthesis pathway as well as identified an Abc1 protein with pleitropic contributions to cell surface functions.
2024-11-06 | GSE265973 | GEO
Project description:Kidneys are pivotal organ in iron redistribution and can be severely damaged in the course of hemolysis. In our previous studies, we observed that induction of hyper- tension with angiotensin II (Ang II) combined with simvastatin administration results in a high mortality rate or the appearance of signs of kidney failure in heme oxy- genase-1 knockout (HO-1 KO) mice. Here, we aimed to address the mechanisms underlying this effect, focusing on heme and iron metabolism. We show that HO-1 deficiency leads to iron accumulation in the renal cortex. Higher mortality of Ang II and simvastatin-treated HO-1 KO mice coincides with in- creased iron accumulation and the upregulation of mucin-1 in the proximal convoluted tubules. In vitro studies showed that mucin-1 hampers heme- and iron-related oxidative stress through the sialic acid residues. In parallel, knock-down of HO-1 induces the glutathione pathway in an NRF2-depedent manner, which likely protects against heme-induced toxicity. To sum up, we showed that heme degradation during heme overload is not solely dependent on HO-1 enzymatic activity, but can be modulated by the glutathione pathway. We also identified mucin-1 as a novel redox regulator. The results suggest that hypertensive patients with less active HMOX1 alleles may be at higher risk of kidney injury after statin treatment.
2023-06-19 | PXD042995 | Pride
Project description:Heme Oxygenase-1 (HO-1) is expressed in many cancers and influences the growth, survivall and metastasis of tumors, however, the molecular mechanisms remains largely unknown. To identify a common mechanism of action of HO-1 in cancer, we studied the global effect of HO-1 on the transcriptome of multiple tumors. Genome-wide expression profiling of HO-1 expressing versus HO-1 silenced cancer cells and a further data mining analysis of the preexisting expression database of 190 human tumors of 14 cancer types led us to identify 14 genes, the expression of which correlated firmly and universally with that of HO-1 (P < 0.001). These genes included regulators of cell plasticity and extracellular matrix remodeling (MMP2, ADAM8, TGFβ1, BGN, COL21A1, PXDN), signaling (CRIP2, MICB), amino acid transport and glycosylation (SLC7A1 and ST3GAL2), estrogen and phospholipid biosynthesis (AGPAT2 and HSD17B1), protein stabilization (IFI30) and phosphorylation (ALPPL2). PXDN, one of the genes being co-expressed with HO-1, was selected for further analysis. Immunofluorescence and western blotting confirmed positive correlation of PXDN with HO-1 levels in BeWo cancer cells as well as co-localization in invasive extravillous trophoblast cells of first trimester placenta. Loss of HO-1 in BeWo cells correlated with reduced cell adhesion to Collagen type I, Fibronectin and Laminin. The adhesion-promoting effects of HO-1 were dependent on PXDN expression, as loss of PXDN in HO-1 expressing BeWo cells led to reduced cell attachment to Laminin and Fibronectin coated wells.
2011-02-15 | GSE20404 | GEO
Project description:The aim was to determine the effect of heme oxygenase-1 (HO-1) overexpression on microRNA transcriptome in human non-small cell lung carcinoma cell line (NCI-H292). Since the cells of different HO-1 genotypes were used (cells are after retroviral transduction with empty vector with normal level of HO-1 or retroviral transduction with vector harboring HO-1), it is possible get the comprehensive answer which microRNAs are regulated by HO-1. Confluent NCI-H292 cells that contain EV-ctrl or overexpressing HO-1. Pool of reference cells are cells untreated and treated with 10 ng/ml TNF-M-NM-1 for 6 hours before RNA isolation. The samples are biological triplicates - three independent experiments were performed at different time points for all cell lines. Total number of the presented samples is 6.
2013-04-27 | E-GEOD-37779 | biostudies-arrayexpress
Project description:We examined, through an oligonucleotide microarray protocol, the renal differential transcriptome profiles of mices submitted to IRI, IPC and Hemin treatment. After identifying the profiles of differentially expressed genes observed for each comparison, we carried out functional enrichment analysis to reveal transcripts putatively involved in potential relevant biological processes and signaling pathways. The most relevant enriched biological processes found in these comparisons were stress, inflammation, apoptosis, pathways in cancer, differentiation, angiogenesis, focal adhesion, ECM-receptor interaction, ion transport, angiogenesis, mitosis and cell cycle, inflammatory response, olfactory transduction and regulation of actin cytoskeleton. In addition, the most important overrepresented pathways were MAPK, ErbB, JAK/STAT, Toll and Nod like receptors, Angiotensin II, Arachidonic acid metabolism, Wnt and coagulation cascade. Also, new insights were gained about the underlying protection mechanisms against renal IRI promoted by IPC and Hemin treatment. Venn diagram analysis allowed us to uncover common and exclusively differentially expressed genes between these two protective maneuvers, underscoring potential common and exclusive biological functions regulated in each case. In summary, IPC exclusively regulated the expression of genes belonging to stress, protein modification and apoptosis, highlighting the role of IPC in controlling exacerbated stress response. Treatment with the Hmox1 inducer Hemin, in turn, exclusively regulated the expression of genes associated with cell differentiation, metabolic pathways, cell cycle, mitosis, development, regulation of actin cytoskeleton and arachidonic acid metabolism, suggesting a pleiotropic effect for Hemin. According to surgery and treatment procedures, mices were divided into five groups: Control, Ischemia-reperfusion injury (IRI), animals pre-treated with Hemin followed by IRI (Hemin + IRI), animals only treated with Hemin (Hemin) and animals pre-conditioned and submitted to IRI (IPC+IRI). To identify the consequences of IRI, Hemin treatment or IPC in gene expression profiles, the following statistical comparisons were made between the groups: IRI vs Control, IPC+IRI vs Control, IPC+IRI vs IRI, IRI+Hemin vs IRI and Hemin vs Control.
2012-12-10 | E-GEOD-39548 | biostudies-arrayexpress
Project description:Heme Oxygenase-1 (HO-1) is expressed in many cancers and influences the growth, survivall and metastasis of tumors, however, the molecular mechanisms remains largely unknown. To identify a common mechanism of action of HO-1 in cancer, we studied the global effect of HO-1 on the transcriptome of multiple tumors. Genome-wide expression profiling of HO-1 expressing versus HO-1 silenced cancer cells and a further data mining analysis of the preexisting expression database of 190 human tumors of 14 cancer types led us to identify 14 genes, the expression of which correlated firmly and universally with that of HO-1 (P < 0.001). These genes included regulators of cell plasticity and extracellular matrix remodeling (MMP2, ADAM8, TGFβ1, BGN, COL21A1, PXDN), signaling (CRIP2, MICB), amino acid transport and glycosylation (SLC7A1 and ST3GAL2), estrogen and phospholipid biosynthesis (AGPAT2 and HSD17B1), protein stabilization (IFI30) and phosphorylation (ALPPL2). PXDN, one of the genes being co-expressed with HO-1, was selected for further analysis. Immunofluorescence and western blotting confirmed positive correlation of PXDN with HO-1 levels in BeWo cancer cells as well as co-localization in invasive extravillous trophoblast cells of first trimester placenta. Loss of HO-1 in BeWo cells correlated with reduced cell adhesion to Collagen type I, Fibronectin and Laminin. The adhesion-promoting effects of HO-1 were dependent on PXDN expression, as loss of PXDN in HO-1 expressing BeWo cells led to reduced cell attachment to Laminin and Fibronectin coated wells. We used gene expression profiling to determine the genome-wide effect of HO-1 on the transcriptome of BeWo trophoblast cells. We specifically selected BeWo cells for our studies because these cells express HO-1 naturally. We knocked down endogenous HO-1 in BeWo cells using retroviral transduction with a micro-RNA adapted retroviral vector targeting human HO-1 sequence. RNA isolated from control (LMP) or miHO1 infected (miHO-1) cells was labeled and hybridized to human genome-wide gene level 1.0 ST arrays
2011-02-15 | E-GEOD-20404 | biostudies-arrayexpress