Exosomes Facilitate Therapeutic Targeting of STAT3 in Liver Fibrosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA637432 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11929036_1.fastq.gz | Fastqsanger.gz | |||
| SRR11929036_2.fastq.gz | Fastqsanger.gz | |||
| SRR11929037_1.fastq.gz | Fastqsanger.gz | |||
| SRR11929037_2.fastq.gz | Fastqsanger.gz | |||
| SRR11929038_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 96 |
Similar Datasets
Project description:Hepatic fibrosis is a wound healing process which results in excessive accumulation of extracellular matrix (ECM) in response to chronic hepatic injury. To determine the impact of iExosomes treatment on target cells gene expression, we extracted total RNA was from livers using TRIzol and purified according to manufacturer instructions. RNA integrity was determined using RNA 6000 Nano Assay by the MDACC Sequencing and ncRNA Program core. Liver RNA sequencing was performed using Illumina TrueSeq stranded mRNA seq MDACC Sequencing and ncRNA Program core. Genome mapping was performed using TopHat software. We found that siSTAT3 iExosomes treatment increased the expression of 1918 genes and decreased expression of 2460 genes, whereas STAT3 mASO iExosomes treatment increased the expression of 2140 genes and decreased expression of 2021 genes. Our results indicate STAT3 is an important ECM deposition relevant-gene for future clinical treatment.
2021-03-19 | GSE151851 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a fatal form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue becomes stiff and losses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-derived conditioned media (LSC-CM) and exosomes (LSC-EXO) to treat different rodent models of lung injury and fibrosis. Inhalation treatment was given for seven consecutive days via a nebulizer for clinical relevance. Results revealed that LSC-CM and LSC-EXO treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure, decreasing collagen accumulation, and myofibroblast proliferation. In addition, LSC-CM and LSC-EXOs exhibited superior therapeutic benefits than their counterparts derived from bone marrow mesenchymal stem cells. LSC-CM and LSC-EXOs provide promising therapeutic options for pulmonary fibrosis.
2019-11-18 | GSE136263 | GEO
Project description:The goal of this study was to understand the effect of human adipose stem cell and its derived exosomes on mouse chronic liver fibrosis. After eight weeks of intraperitoneal injection of CCl4, we treated 200μl PBS, normal human adipose stem cell (1×106/200μl PBS), human adipose stem cell-derived exosomes(250μg/200μl PBS) once a week for 4 weeks. Then the livers were collected and isolated RNA for RNA-sequencing to explore alterations in mRNA expression between different treatments
2022-04-02 | GSE199732 | GEO
Project description:Mechanism for Human Adipose Stem Cell-Derived Exosomes' Therapeutic Effect on Chronic Liver Fibrosis
| PRJNA821315 | ENA
Project description:Background and aims: Signal transducer and activator of transcription 3 (Stat3) is the main mediator of interleukin-6 type cytokine signaling required for hepatocyte proliferation and hepatoprotection but its role in sclerosing cholangitis and other cholestatic liver diseases remains unresolved. Methods: We investigated the role of Stat3 in inflammation-induced cholestatic liver injury and used mice lacking the multidrug resistance gene 2 (mdr2-/-) as a model for SC. Results: We demonstrate that conditional inactivation of stat3 in hepatocytes and cholangiocytes (stat3 delta hc) of mdr2-/- mice strongly aggravated bile acid-induced liver injury and fibrosis. A similar phenotype was observed in mdr2-/- mice lacking IL-6 production. Biochemical and molecular characterization suggested that Stat3 exerts hepatoprotective functions in both, hepatocytes and cholangiocytes. Loss of Stat3 in cholangiocytes led to increased expression of TNFα which might reduce the barrier function of bile ducts. Loss of Stat3 in hepatocytes led to upregulation of bile acid biosynthesis genes and downregulation of hepatoprotective epidermal growth factor receptor and insulin-like growth factor 1 signaling pathways. Consistently, stat3deltahc mice were more sensitive to cholic acid-induced liver damage than control mice. Conclusions: Our data suggest that Stat3 prevents cholestasis and liver damage in sclerosing cholangitis via regulation of pivotal functions in hepatocytes and cholangiocytes. Affymetrix microarray analyses was performed to identify metabolic and molecular pathways in stat3Dhc mdr2-/- mice that lead to cholestasis and bile acid-induced liver injury. To avoid false positive results that are due to differential cellular composition, we defined the onset of fibrosis and expression of fibrogenic factors in stat3Dhc mdr2-/- mice.
2010-10-20 | E-GEOD-18759 | biostudies-arrayexpress
Project description:Macrophages are recognized as the vital players in renal fibrosis, with a high degree of heterogeneity and plasticity, and triggering receptor expressed on myeloid cell-2(TREM-2) was highly expressed on macrophages and participated in the progression of tissue fibrosis. However, the mechanism by which TREM-2 mediate the progress of renal fibrosis is still unclear. Our study have found the exosomes derived from TREM-2 deficient (TREM-2-/-) macrophages could suppress the progression of fibrosis, showing a higher matrix metalloproteinase-9 (MMP-9) / tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) ration at protein level in secreted exosomes than exosomes from WT（wild type）macrophages in the fibrotic microenvironment. Besides, renal tubular epithelial cells (TECs) engulfed theses nanoscale vesicles, the expression of collagen I and α-smooth muscle actin (α-SMA) (fibrosis related marker) was obviously decreased. Through the RNA-seq, we found that TREM-2-/- macrophages upregulate the MMP-9/TIMP-1 ratio in its exosomes via HSPa1b/AKT pathway. Furthermore, it’s noteworthy that the renal fibrosis was effectively alleviated in the obstructed kidney from mice received a renal pelvis injection of adeno associated virus (AAV-shTREM-2) containing the sequence of silencing TREM-2. However, VER-155008 (inhibitor of HSPa1b) and Ly294002 (inhibitor of AKT) reversed this effect. Moreover, polyclonal antibodies against TREM-2 also effectively relieved the UUO-induced renal fibrosis. Above all, we have validated that the knocking down TREM-2 expression can inhibit the progression of renal fibrosis through a macrophage exosome-dependent pathway in vitro and vivo. Hence, our finding suggest TREM-2 is potential therapeutic target for CKD.
2024-11-29 | GSE262665 | GEO
Project description:Cystic Fibrosis is a life limiting disease due to mutations in the Cystic Fibrosis Conductance Gene Regulator (CFTR). This is associated with a multiorgan disease combining pancreatic insufficiency, chronic infected bronchopathy and production of a salty sweat. Increased survival of patients leads to observation of new complications, including proximal tubule transport dysfunctions with increased output of glucose, amino acids, phosphate, calcium, uric acid, and low Molecular Weight proteins, which ultimately triggers tubulo-interstitial injury and chronic kidney disease. (Jouret et al. 2007) Exosomes are membrane vesicles stemming from Multi-Vesicular Bodies. They reflect the biological state of the cell they stem from because they incorporate various bioactive molecules from their cell of origin, which can be transferred to target cells. They are therefore ideal biomarkers for early diagnosis, prediction of disease progression or response to treatment. Urinary exosomes have been largely investigated in kidney or urothelial diseases and exosomal proteins proved to be biomarkers reflecting renal cellular biology. We hypothetized that urinary exosomal proteins might be differentially expressed, according to the presence of the mutation in the CFTR gene and its correction. We analyzed urinary exosomes of patients with CF and healthy controls based on their protein content determined by high resolution mass spectrometry, in combination with Gene Set Enrichment Analysis. These results were compared to those obtained in exosomes collected in patients treated with CFTR modulators.
2021-03-29 | PXD018537 | Pride
Project description:Lung cancer is a fatal complication of idiopathic pulmonary fibrosis (IPF) with a poor prognosis. Current treatments are insufficient in improving the prognosis of lung cancer patients with comorbid idiopathic pulmonary fibrosis (IPF-LC). Senescent fibroblasts play a pivotal role within the tumor microenvironment, influencing tumor progression by secreted exosomes. With evidence that fibroblast senescence is an important mechanism of IPF, we sought to investigate the impact of senescent IPF lung fibroblast-derived exosomes on non-small cell lung cancer (NSCLC). Our results show that IPF fibroblasts (diseased human lung fibroblasts, DHLF) express significant senescence markers, promoting NSCLC proliferation, invasion, and epithelial-mesenchymal transition. Specifically, we observed senescent DHLFs secret more exosomes (DHLF-exosomes), which could enhance proliferation and colony-forming ability of cancer cells. Proteomic analysis of DHLF-exosomes identified upregulation of SASP factors, notably MMP1, which activates the surface receptor PAR1. Knocking down MMP1 or using PAR1 inhibitors reduced the tumor-promoting effects of DHLF-exosomes in vivo and in vitro. Mechanistically, MMP1 acted via activating the PI3K-AKT-mTOR pathway. In conclusion, our results suggest that exosomal MMP1 derived from senescent IPF fibroblasts promotes NSCLC proliferation and colony formation by targeting PAR1 and activating the PI3K-AKT-mTOR pathway. These findings provide a novel therapeutic approach for patients with IPF-LC.
2024-10-21 | GSE279637 | GEO
Project description:Exosomes from MSC facilitate diabetic wound healing by promoting angiogenesis
| PRJNA812774 | ENA
Project description:Gp130 receptor engagement on neoplastic cells provides a link by which an inflammatory microenvironment facilitates tumour promotion. Although hyperactivation of the gp130-dependent Stat3 signalling node is commonly observed in solid tumours, Stat3 remains a challenging therapeutic target. To mimic excessive Stat3 signalling, we molecularly validate the gp130FF mouse as a preclinical model for inflammation-associated intestinal-type gastric cancer (IGC), with aberrant mammalian target of rapamycin (mTOR) pathway activity as shared feature. Accordingly, administration of the mTorc1 inhibitor RAD001 reversibly reduced IGC burden in gp130FF mice and suppressed colitis-associated cancer in wild-type mice. Since the therapeutic effect of RAD001 occurs independently of Stat3 hyperactivation, which is also dispensable for gp130-dependent engagement of the PI3K/Akt/mTorc1 pathway, we conclude that mTorc1 signalling limits tumour promoting Stat3 activity The mouse whole-genome gene expression profiling was performed on Illumina's MouseWG-6 v2.0 Expression BeadChips for 24 mice, with 8 mice in each group (gp130WT antral tissue, gp130FF unaffected antral tissue and gp130FF tumour tissue).
2013-01-29 | E-GEOD-35808 | biostudies-arrayexpress