HO-1 attenuates testicular ischaemia/reperfusion injury by activating the phosphorylated C-jun-miR-221/222-TOX pathway
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ABSTRACT:
SUBMITTER: Xie B
PROVIDER: S-EPMC10839873 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-02-14 | GSE237565 | GEO
Project description:Heme oxygenase(HO-1) has been shown to protect against I/R injury, but its effects on testicular I/R is very limited. Therefore, this study aims to investigate the effects of HO-1 on testicular I/R and the underlying mechanism.Knockout of HO-1 rats by TALEN technique.Immunofluorescence and immunohistochemistry was used to detect HO-1 nuclear translocation. Flow cytometry was used to detect cell apoptosis and cell cycle.High-resolution miRNA,mRNA sequencing, real-time PCR and western blot were performed to select testicular I/R injury related genes with strong conservation in HO-1 knockout rats.Double luciferase reporter assay was used to verify the relationship between c-Jun and miR-221/222.We found that HO-1 improved the pathological damage caused by testicular I/R in vivo. We verified the nuclear translocation of HO-1 and its protective effect on hypoxia/reoxygenation(H/R) damage in GC-1 cells.And our results indicated that HO-1 protein itself rather than heme breakdown metabolites might play a key role in testicular I/R.Gene sequencing was performed to screen out MiR221/222 and its downstream gene-thymocyte selection associated high mobility group box(TOX). In addition, we found that HO-1 increased phosphorylation of c-Jun in H/R group.We knocked down c-Jun in GC-1 cells and observed a decrease in the expression of miR-221/222.And we found by inhibiting HO-1,we observed a decrease in the expression of c-jun and miR-221/222,which could be rescued by adding c-jun. The dual luciferase reporter assay confirmed the interaction between c-Jun and miR-221/222. Collectively, HO-1 possesses a protective effect on testicular I/R via phosphorylated c-Jun-miR-221/222-TOX pathway.
2024-02-14 | GSE236536 | GEO
Project description:Heme oxygenase(HO-1) has been shown to protect against I/R injury, but its effects on testicular I/R is very limited. Therefore, this study aims to investigate the effects of HO-1 on testicular I/R and the underlying mechanism.Knockout of HO-1 rats by TALEN technique.Immunofluorescence and immunohistochemistry was used to detect HO-1 nuclear translocation. Flow cytometry was used to detect cell apoptosis and cell cycle.High-resolution miRNA,mRNA sequencing, real-time PCR and western blot were performed to select testicular I/R injury related genes with strong conservation in HO-1 knockout rats.Double luciferase reporter assay was used to verify the relationship between c-Jun and miR-221/222.We found that HO-1 improved the pathological damage caused by testicular I/R in vivo. We verified the nuclear translocation of HO-1 and its protective effect on hypoxia/reoxygenation(H/R) damage in GC-1 cells.And our results indicated that HO-1 protein itself rather than heme breakdown metabolites might play a key role in testicular I/R.Gene sequencing was performed to screen out MiR221/222 and its downstream gene-thymocyte selection associated high mobility group box(TOX). In addition, we found that HO-1 increased phosphorylation of c-Jun in H/R group.We knocked down c-Jun in GC-1 cells and observed a decrease in the expression of miR-221/222.And we found by inhibiting HO-1,we observed a decrease in the expression of c-jun and miR-221/222,which could be rescued by adding c-jun. The dual luciferase reporter assay confirmed the interaction between c-Jun and miR-221/222. Collectively, HO-1 possesses a protective effect on testicular I/R via phosphorylated c-Jun-miR-221/222-TOX pathway.
2024-02-14 | GSE237563 | GEO
Project description:HO-1 attenuates testicular ischemia/reperfusion injury through activating the phosphorylated c-Jun-miR-221/222-TOX pathway
| PRJNA995743 | ENA
Project description:HO-1 attenuates testicular ischemia/reperfusion injury through activating the phosphorylated c-Jun-miR-221/222-TOX pathway [miRNA]
| PRJNA991541 | ENA
Project description:HO-1 attenuates testicular ischemia/reperfusion injury through activating the phosphorylated c-Jun-miR-221/222-TOX pathway [lncRNA+circRNA]
| PRJNA995747 | ENA
Project description:Cardiovascular disease is a major health problem in industrialized and developing countries and is the leading cause of death and disability. Myocardial ischemia/reperfusion (I/R) causes cardiomyocyte damage such as apoptosis and hypertrophy. The purpose of this study was to investigate the effects of exosomes from adipose-derived stem cells (ADSC-Exo) on hearts from I/R mice and to explore the underlying mechanisms. ADSC-Exo significantly decreased I/R-induced cardiomyocyte apoptosis and hypertrophy, as detected by TdT-mediated dUTP nick end-labeling (TUNEL) and wheat germ agglutinin (WGA) staining, respectively. In addition, the expression of apoptosis-related proteins p-p53 and PUMA and hypertrophy-related proteins ETS-1 and ANP were significantly reduced in the cardiomyocytes of ADSC-Exo-treated I/R mice compared to those of control mice. Both PUMA and ETS-1 are reported to be target genes for miR-221/222. I/R operation significantly reduced miR-221/222 expression, while ADSC-Exo treatment increased miR-221/222 expression, as detected by RT-qPCR. We also observed that cardiac I/R operation markedly increased cell apoptosis and hypertrophy in miR-221/222 knockout (KO) mice, while ADSC-Exo reduced the effects of I/R operation. Furthermore, ADSC-Exo protected H9c2 cardiomyocytes from H2O2-induced damage by reducing apoptosis and hypertrophy in vitro. H2O2 treatment significantly reduced miR-221/222 expression, while ADSC-Exo treatment reversed this effect in H9c2 cells. ADSC-Exo treatment decreased H2O2-induced PUMA and ETS-1 expression. Compared with control treatment, I/R treatment significantly reduced p-AKT and increased p-p65, while ADSC-Exo and miR-221/222 mimics attenuated these effects. The AKT activator SC79 and p65 inhibitor Bay 11-7082 reduced H2O2-induced cell apoptosis and hypertrophy. Based on these findings, ADSC-Exo prevents cardiac I/R injury through the miR-221/miR-222/PUMA/ETS-1 pathway. Therefore, ADSC-Exo is an effective inhibitor of I/R-induced heart injury.
| S-EPMC7744807 | biostudies-literature
Project description:Oxidative stress is considered a key factor contributing to the initiation and development of cardiac injury following ischaemia‒reperfusion (I/R). Arachidonate 5-lipoxygenase (ALOX5) is a rate-limiting enzyme for leukotriene biosynthesis. MK-886 is an inhibitor of ALOX5 that exhibits anti-inflammatory and antioxidant activities. However, the significance of MK-886 in preventing I/R-mediated cardiac injury and the underlying mechanism remain unclear. Cardiac I/R model was produced by ligation/release of the left anterior descending artery. MK-886 (20 mg/kg) was administered intraperitoneally into mice at 1 and 24 h before I/R. Our results indicated that MK-886 treatment significantly attenuated I/R-mediated cardiac contractile dysfunction and decreased the infarct area, myocyte apoptosis, and oxidative stress accompanied with reduction of Kelch-like ECH-associated protein 1 (keap1) and upregulation of nuclear factor erythroid 2-related factor 2 (NRF2). Conversely, administration of the proteasome inhibitor epoxomicin and NRF2 inhibitor ML385 greatly abrogated MK-886-mediated cardioprotection after I/R injury. Mechanistically, MK-886 enhanced the expression of the immunoproteasome subunit β5i, which interacted with keap1 and enhanced its degradation, leading to activation of the NRF2-dependent antioxidant response and improvement of mitochondrial fusion-fission balance in the I/R-treated heart. In summary, our present findings indicated that MK-886 could protect the heart against I/R injury and highlight that MK-886 may represent a promising therapeutic candidate for preventing ischaemic disease.
| S-EPMC10149391 | biostudies-literature
Project description:Full title: Expression data from antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells The expression of miR-221/222 were found to be upregulated in fulvestrant resistant breast cancer cells MCF7-FR compared to its drug-sensitive counterpart MCF7. To investigate the role of miR-221/222 in acquired resistance to fulvestrant, we lowered the level of miR-221/222 in MCF7-FR cells using miRNA inhibitors (antagomirs), and compared gene expression profiles before and after treatment. Fulvestrant-resistant breast cancer cells MCF7-FR (originated from drug-sentitive breast cancer model cell line MCF7) were transient-transfected by antigomirs targeting miR221 or miR222 (i.e. si221, si222). All three cell lines, MCF7-FR, siR221, siRNA222 were subjected to gene expression profiling.
| S-ECPF-GEOD-19777 | biostudies-other
Project description:Analysis of gene expression of MCF10A to identify the targets of miR-221 and miR-222 Keywords: MCF10, miR-221, miR-222 RNA profiles of human MCF10A cell line
| S-ECPF-GEOD-29327 | biostudies-other