Amniotic Fluid Reduces Liver Fibrosis By Attenuating Hepatic Stellate Cell Activation
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ABSTRACT:
PROVIDER: PRJNA1225741 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32401200_1.fastq.gz | Fastqsanger.gz | |||
| SRR32401200_2.fastq.gz | Fastqsanger.gz | |||
| SRR32401201_1.fastq.gz | Fastqsanger.gz | |||
| SRR32401201_2.fastq.gz | Fastqsanger.gz | |||
| SRR32401202_1.fastq.gz | Fastqsanger.gz |
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Project description:Background & Aims: Persistent activation of hepatic stellate cells (HSCs) drives liver fibrosis, marked by myofibroblast activation (MFA) and epithelial-mesenchymal transition (EMT). Strategies to prevent or reverse this will be critical to treat liver fibrosis successfully. We previously showed that full-term, cell-free human amniotic fluid (cfAF) inhibits MFA and EMT in fibroblasts in vitro. We hypothesize that cfAF treatment can attenuate HSC activation and limit liver fibrosis. Methods: HSC activation was assessed using murine models of acute (DMN) and chronic (CCl4) liver damage, three-dimensional hepatic spheroids, and HSC cultures. EMT and MFA were induced in vitro using ethanol (spheroids) or TGFβ (HSCs) and evaluated via scratch assays, multi-omics approaches, and RNA/protein analyses. Results: cfAF treatment prevented weight loss in mice with chronic liver damage without adverse events. Histological analysis revealed a modest reduction in fibrosis with preserved liver architecture in both chronic and acute murine liver damage models. Gene expression profiling and immunostaining indicated cfAF administration to CCl4-treated mice led to reduced EMT- and MFA-related biomarkers along with changes in transcripts associated with liver metabolism, immune regulatory pathways, and cell signaling. In hepatic spheroids exposed to ethanol cfAF treatment lowered COL1A1 protein levels and smooth muscle actin (SMA) RNA abundance in a dose-dependent manner. Treating primary or LX2 hepatic stellate cells with cfAF strongly represses EMT, and multi-omics analyses revealed that it also attenuates TGFβ-induced MFA and the inflammatory phenotype. Thus cfAF treatment prevents liver fibrosis by safeguarding hepatic stellate cell activation. Conclusions: cfAF treatment limits liver fibrosis by repressing HSC activation in liver fibrosis models. These findings suggest cfAF may be a safe and effective therapy for reducing liver fibrosis and preventing the development of cirrhosis and/or hepatocellular carcinoma.
2025-03-17 | GSE290015 | GEO
Project description:Microarray data comparison of amniocytes, amniotic fluid-iPSCs, and cardiomyocyte derivatives
2016-01-20 | GSE76965 | GEO
Project description:Regardless of the source of injury or metabolic dysfunction, fibrosis is a frequent driver of liver pathology. Excessive liver fibrosis is caused by persistent activation of hepatic stellate cells (HSCs), which is defined by myofibroblast activation (MFA) and the epithelial-mesenchymal transition (EMT). Strategies to prevent or reverse this HSC phenotype will be critical for successful treatment of liver fibrosis. We have previously shown that full-term, cell-free human amniotic fluid (cfAF) inhibits MFA and EMT in fibroblasts in vitro. We hypothesize that cfAF treatment can attenuate HSC activation and limit liver fibrosis. We tested if cfAF could prevent liver fibrosis or HSC activation in murine models of liver damage, three-dimensional hepatic spheroids, and HSC cultures. Administering cfAF prevented weight loss and the extent of fibrosis in mice with chronic liver damage without stimulating deleterious immune responses. Gene expression profiling and immunostaining indicated that cfAF administration in carbon tetrachloride-treated mice reduced EMT- and MFA-related biomarker abundance and modulated transcript levels associated with liver metabolism, immune regulatory pathways, and cell signaling. cfAF treatment lowered MFA biomarker levels in a dose-dependent manner in hepatic spheroids exposed to ethanol. Treating HSCs with cfAF in vitro strongly repressed EMT. Multi-omics analyses revealed that it also attenuates TGFβ-induced MFA and inflammation-associated processes. Thus, cfAF treatment prevents liver fibrosis by safeguarding against persistent HSC activation. These findings suggest that cfAF may be a safe and effective therapy for reducing liver fibrosis and preventing the development of cirrhosis and/or hepatocellular carcinoma.
| S-EPMC11870538 | biostudies-literature
Project description:Fetal wounds repair by regeneration rather than wound healing and the environment is dominated by amniotic fluid. We are looking at early transcriptional regulation of keratinocytes cultured in amniotic fluid in vitro. Keratinocytes were isolated and expanded to passage three after which they were starved in DMEM for 12h then cultured for 24h in human amniotic fluid (50%), fcs (50%) or DMEM alone for another 24h. N=2, pooled replicates per CEL-file.
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Project description:Intra-amniotic infection, the invasion of microbes into the amniotic cavity resulting in an inflammatory process, is a clinical condition that can lead to adverse pregnancy outcomes for the mother and fetus as well as severe long-term neonatal morbidities. Despite much research focused on the consequences of intra-amniotic infection, there is still little knowledge about the functional roles of innate immune cells that respond to invading microbes. In the current study, we performed RNA sequencing of sorted neutrophils and monocytes/macrophages from amniotic fluid from women with intra-amniotic infection to determine the transcriptomic differences between these innate immune cells. Further, we sought to identify specific transcriptomic pathways that were significantly altered by the maternal or fetal origin of amniotic fluid neutrophils and monocytes, the presence of a severe fetal inflammatory response, and pregnancy outcome (i.e. preterm or term delivery). We showed that significant transcriptomic differences exist between amniotic fluid neutrophils and monocytes/macrophages from women with intra-amniotic infection that are indicative of the distinct roles these cells play. We also found that amniotic fluid monocytes/macrophages of fetal origin display impaired ability to clear out microbes invading the amniotic cavity compared to those of maternal origin. Notably, we demonstrate that the transcriptomic changes in amniotic fluid monocytes/macrophages are heavily associated with the severity of the fetal inflammatory response, suggesting that the trafficking of fetal neutrophils throughout the umbilical cord is partially modulated by monocytes/macrophages in the amniotic cavity. Finally, we show that amniotic fluid neutrophils and monocytes/macrophages from preterm deliveries display enhanced transcriptomic activity compared to those from term deliveries, highlighting the protective role of these innate immune cells in this vulnerable period. Collectively, these findings demonstrate the underlying complexity of local innate immune responses in women with intra-amniotic infection, and provide new insights into the functions of amniotic fluid neutrophils and monocytes in the amniotic cavity.
2023-01-05 | GSE222204 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE30064: Cultured human amniotic fluid-derived mesenchymal stromal cells [PIQOR data] GSE30065: Cultured human amniotic fluid-derived mesenchymal stromal cells [miRXplore data] Refer to individual Series
2011-06-18 | E-GEOD-30066 | biostudies-arrayexpress
Project description:The objective of this study was to identify the tissue expression patterns and biological pathways enriched in term amniotic fluid cell-free fetal RNA by comparing functional genomic analyses of term and second-trimester amniotic fluid supernatants. There were 2,871 significantly differentially regulated genes. In term amniotic fluid, tissue expression analysis showed enrichment of salivary gland, tracheal, and renal transcripts as compared with brain and embryonic neural cells in the second trimester. Functional analysis of genes upregulated at term revealed pathways that were highly specific for postnatal adaptation such as immune function, digestion, respiration, carbohydrate metabolism, and adipogenesis. Inflammation and prostaglandin synthesis, two key processes involved in normal labor, were also activated in term amniotic fluid. This was a prospective whole genome microarray study comparing eight amniotic fluid samples collected from eight women at term who underwent prelabor cesarean delivery and eight second-trimester amniotic fluid samples from routine amniocenteses. A functional annotation tool was used to compare tissue expression patterns in term and second-trimester samples. Pathways analysis software identified physiologic systems, molecular and cellular functions, and upstream regulators that were significantly overrepresented in term amniotic fluid.
2013-04-23 | E-GEOD-46286 | biostudies-arrayexpress
Project description:The objective of this study was to identify the tissue expression patterns and biological pathways enriched in term amniotic fluid cell-free fetal RNA by comparing functional genomic analyses of term and second-trimester amniotic fluid supernatants. There were 2,871 significantly differentially regulated genes. In term amniotic fluid, tissue expression analysis showed enrichment of salivary gland, tracheal, and renal transcripts as compared with brain and embryonic neural cells in the second trimester. Functional analysis of genes upregulated at term revealed pathways that were highly specific for postnatal adaptation such as immune function, digestion, respiration, carbohydrate metabolism, and adipogenesis. Inflammation and prostaglandin synthesis, two key processes involved in normal labor, were also activated in term amniotic fluid.
2013-04-23 | GSE46286 | GEO
Project description:Amniotic fluid stem cells (AFSCs) are of interest in regenerative medicine as a non-controversial and potentially 'abundant' source of stem cells. Progress has been made in understanding amniotic fluid stem cell biology, and amniotic fluid-derived cells have been induced to form neurons, osteoblasts, muscle cells, and others. Our study evaluates change in the genome-wide expression profile of amniotic fluid stem cells during in-vitro culture, using Affymetrix U133 Plus 2.0 microarray chips. We found that only 3.08% of gene probes were differentially expressed from early to late passage of AFSC culture. The differentially expressed genes were related to biological processes or cellular function - including transcription factors, protein kinases, and cytokines/growth factors. Other gene-sets of interest were oncogenes and tumor suppressor genes, which were a very small number of genes. We further analyzed the gene sets of interest using NIH DAVID and GSEA bioinformatics databases for gene annotations analysis. Applying false discovery rate correction, there was no significant difference in the genome-wide expression profiling between early and late passage. AFSCs maintain their genome-wide expression profile during in-vitro culture. Amniotic fluid-derived c-kit-positive cells were maintained in stem cell culture and genome-wide expression changes were studied and compared between early passage and late passage in culture.
2012-08-02 | E-GEOD-39839 | biostudies-arrayexpress