The difference of placental fibroblast between normal pregnancy and preeclampsia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE99007 | GEO | 2017/05/18
SECONDARY ACCESSION(S): PRJNA386986
REPOSITORIES: GEO
Similar Datasets
Project description:Preeclampsia (PE) is a pregnancy disorder characterized by high blood pressure and proteinuria that can cause adverse health effects in both mother and fetus. There is no current cure for PE other than delivery of the fetus. While the etiology is unknown, poor placentation of the placenta due to aberrant signaling of growth and angiogenic factors has been postulated as causal factors of PE. In addition, environmental contaminants, such as the metal cadmium (Cd), have been linked to placental toxicity and increased risk of developing PE. Here, we use a translational study design to investigate genomic and epigenomic alterations in both placentas and placental trophoblasts, focused on the angiogenesis-associated transforming growth factor-beta (TGF-β) pathway. Genes within the TGF-β pathway displayed increased expression in both the preeclamptic placenta and Cd-treated trophoblasts. In addition, miRNAs that target the TGF-β pathway were also significantly altered within the preeclamptic placenta and Cd-treated trophoblasts. Integrative analysis resulted in the identification of a subset of Cd-responsive miRNAs, including miR-26a and miR-155, common to preeclamptic placentas and Cd-treated trophoblasts. These miRNAs have previously been linked to PE and are predicted to regulate members of the TGF-β pathway. Results from this study provide future targets for PE treatment.
2016-07-12 | GSE84260 | GEO
Project description:Myocardial infarctions cause hypoxic injury to downstream tissue and a consequent fibrotic remodeling process to replace injured tissue with a scar. Scar formation occurs through phases of wound healing in which stimuli such as transforming growth factor-beta (TGF-β) drive cardiac fibroblasts to activate into a myofibroblast phenotype and deposit matrix molecules that form a scar. While this is necessary to repair injured tissue, excessive fibrosis commonly occurs which is correlated with heart failure. Therefore, defining cardiac fibroblast phenotypes under hypoxic stimuli and TGF-β is essential for understanding and treating pathological fibrosis. We robustly characterized fibroblast phenotype through immunofluorescence, quantitative RT-PCR, and proteomic analysis, after either TGF-β treatment or hypoxia durations that mimic acute hypoxic injury post-infarction. We find that hypoxic fibroblasts respond to low oxygen with increased hypoxia inducible factor 1 (HIF-1) but not HIF-2 activity by 4h. This is accompanied by increased gene and protein levels of VEGFA and LOX, respectively, which are both targets of HIF-1. Both TGF-β1 and hypoxia inhibit proliferation by 24h. While TGF-β1 treatment upregulated various fibrotic pathways, hypoxia causes a global reduction in protein synthesis, including collagen biosynthesis. This study discerns overlapping from distinctive outcomes of TGF-β1 and hypoxia treatment, which is important for elucidating their roles in fibrotic remodeling post-MI.
2024-07-03 | PXD051197 | Pride
Project description:Preeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are major contributor of perinatal morbility and mortality, these pregnancy disorders associated with placental ischemia and share many similar pathophysiological features. The aim of this study was to compare the placental gene expression profiles including mRNA and lnRNAs from pregnant women from four study groups; PE, IUGR, PE-IUGR and normal pregnancy (NP). Gene expression microarray analysis was performed on placental tissue obtained at the moment of delivery and results were validated using RTq-PCR. Differential gene expression analysis revealed that the largest transcript variation was observed in the IUGR samples compared to NP (n=461; 314 mRNAs: 252 up-regulated and 62 down-regulated) and 133 lncRNAs: 36 up-regulated and 98 down-regulated). We also detected a group of differentially expressed transcripts shared between the PE and IUGR samples compared to NP (n=39), including 9 lncRNAs with a high correlation degree (P <0.05). Functional enrichment of these shared transcripts showed that cytokine signaling pathways, protein modification and regulation of JAK-STAT cascade are over-represented in both placental ischemic diseases. These findings contribute to the molecular characterization of placental ischemia showing common epigenetic regulation implicated in the pathophysiology of preeclampsia and Intrauterine Growth Restriction
2020-05-31 | GSE147776 | GEO
Project description:Background: Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries. The placenta is central to the etiology of PE. However, how and to what extent the placenta contributes to worse PE outcomes in persons of African ancestry is yet to be fully elucidated. Objective: We aimed to identify molecular pathways that are unique or enriched in placentas of parturient persons of African ancestry with PE with severe features (sPE) compared to those of Asian and European ancestry with sPE. Study design: Bulk RNA sequencing was performed on 50 placentas from parturient persons with sPE of African (n=9), Asian (n=18) and European (n=23) ancestries and 73 normotensive controls of African (n=9), Asian (n=15) and European (n=49) ancestries. Results: Metabolism, hormone regulation and hypoxia/angiogenesis genes, previously described to be upregulated in PE, including: LEP, PAPPA2, INHA, FSTL3, FLT1, PHYHIP and ENG, were upregulated in sPE across ancestries, with high expression of FSTL3 being additionally associated with intrauterine growth restriction (p<.0001). Notably, LEP, FLT1 and PHYHIP were more highly upregulated in sPE placentas from parturient persons of African versus Asian ancestry. Genes associated with allograft rejection and adaptive immune response were selectively upregulated in placentas from African ancestry parturitions and not in those of Asian and European ancestries. Among the allograft rejection/adaptive immune response genes, IL3RA was of particular interest because the patient with the highest placental IL3RA level, a woman of African ancestry with IL3RA levels 4.5-fold above the average for African ancestry parturitions with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients of Asian and European ancestries with the highest IL3RA levels for their ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p=.0005). Conclusions: African ancestry parturitions are associated with higher placental upregulation of metabolism (LEP) and hypoxia/angiogenesis (FLT1) genes, and selective upregulation of allograft rejection/adaptive immune response genes, including IL3RA. High placental expression of IL3RA may predict worse maternal cardiovascular outcomes, including peripartum cardiomyopathy. Studies evaluating placental IL3RA levels in peripartum cardiomyopathy cohorts are therefore warranted, as are broader studies evaluating placental factors in maternal cardiovascular outcomes postpartum.
2023-11-09 | GSE234729 | GEO
Project description:Myofibroblast is a specific type of mesenchymal cell characterized by synthesis of extracellular matrix and contractile activity. While it serves a beneficial function during tissue wound healing under physiological conditions, it can cause devastating damage to organs afflicted with fibrosis. Myofibroblasts are also present in tumor stroma and contribute actively to tumor growth and spreading. Chicken embryo dermal myofibroblasts (CEDM) represent a novel ex vivo model suitable for the analysis of myofibroblastic phenotype as they show strongly pronounced, uniform and self-sustained myofibroblastic phenotype that is stable in time. As myofibroblastic differentiation is controlled chiefly by TGF-beta signaling, the understanding of the differentiation program entails the determination of TGF-beta-regulated genes. To achieve such a goal, we performed oligonucleotide microarray analysis of CEDM cells treated with a selective TGFBR1 kinase inhibitor. Genes reported previously to be under the control of TGF-beta signaling in mammalian cells appeared among the affected genes also in CEDM cells and many so far unknown TGF-beta targets were revealed. Comparison of the expression profiles of chicken embryo dermal myofibroblasts in culture treated with TGFBR1 Kinase Inhibitor II or DMSO only. Three biological replicates were analyzed for each group.
2011-04-15 | E-GEOD-28634 | biostudies-arrayexpress
Project description:Preeclampsia (PE), which affects 2-7% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. To better understand the pathophysiology of PE, gene expression profiling of placental tissue from 5 controls and 5 PEs were assessed using microarray. A total of 224 transcripts were identified as being significantly differentially expressed (fold change > 2 and q value < 0.05 in the SAM software), GO enrichment analysis indicated that genes involved hypoxia, oxidative and reductive processes were significantly changed. Ten differentially expressed genes (DEGs) involved in these biological process were further verified by quantitative real-time PCR. Finally, the potential therapeutic agents for PE were explored via Connectivity Map database . In conclusion, the data obtained in this study might provide clues to better understand the pathophysiology of PE and found potential therapeutic agents for PE patients. gene expression profiling of placental tissue from 5 controls and 5 PEs were assessed using microarray.
2013-10-01 | E-GEOD-47187 | biostudies-arrayexpress
Project description:TGF-β stimulates CCN2 expression which in turn amplifies TGF-β signaling. This process promotes extracellular matrix production and accelerates the pathological progression of fibrotic diseases. Alternative splicing plays an important role in multiple disease development, while U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential factor in the early steps of pre-mRNA splicing. However, the molecular mechanism underlying abnormal CCN2 expression upon TGF-β stimulation remains unclear. This study elucidates that SIRT4 acts as a master regulator for CCN2 expression in response to TGF-β by modulating U2AF2-mediated alternative splicing. Analyses of renal biopsy specimens from patients with CKD and mouse fibrotic kidney tissues revealed marked nuclear accumulation of SIRT4. The tubulointerstitial fibrosis was alleviated by global deletion or tubular epithelial cell (TEC)-specific knockout of Sirt4, and aggravated by adeno-associated virus-mediated SIRT4 overexpression in TECs. Furthermore, SIRT4 was found to translocate from the mitochondria to the cytoplasm through the BAX/BAK pore under TGF-β stimulation. In the cytoplasm, TGF-β activated the ERK pathway and induced the phosphorylation of SIRT4 at Ser36, which further promoted its interaction with importin α1 and subsequent nuclear translocation. In the nucleus, SIRT4 was found to deacetylate U2AF2 at K413, facilitating the splicing of CCN2 pre-mRNA to promote CCN2 protein expression. Importantly, exosomes containing anti-SIRT4 antibodies were found to effectively mitigate the UUO-induced kidney fibrosis in mice. Collectively, these findings indicated that SIRT4 plays a role in kidney fibrosis by regulating CCN2 expression via the pre-mRNA splicing.
2024-10-11 | GSE279225 | GEO
Project description:Preeclampsia (PE) has been associated with placental dysfunction, resulting in foetal hypoxia, accelerated erythropoiesis and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and erythroid differentiation capacity of UCB hematopoietic stem/ progenitor cells (HSPCs), UCB erythroid profiles along with transcriptome and proteome of these cells between male and female foetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC migration/ homing and in vitro erythroid colony differentiation, the UCB HSPC transcriptome and the proteomic profile of the in vitro differentiated erythroid cells differed between PE vs normotensive samples. Accordingly, despite absence of significant differences in the UCB erythroid populations in male or female foetuses from PE or normotensive pregnancies, transcriptional changes were observed during erythropoiesis, particularly affecting male foetuses. Pathway analysis suggested deregulation in mTORC1/AMPK signaling pathways controlling cell cycle, differentiation and protein synthesis. These results associate PE with transcriptional and proteomic changes in foetal HSPCs and erythroid cells that may underlie the higher erythroblast count in the UCB in PE.
2019-06-20 | PXD010364 | Pride
Project description:Analysis of transcriptome post hypoxia and TGF-β treatment in breast cancer In order to explore the role of TGF-β signaling in mediating the alternative splicing program in breast cancer, we profiled the pre-mRNA splicing and mRNA gene expression upon hypoxia and TGF-β treatment using Human Transcriptome Array 2.0.
2020-08-24 | GSE147516 | GEO
Project description:To elucidate biological processes underlying the keratocyte, fibroblast, and myofibroblast phenotypes of corneal stromal cells, the gene expression patterns of these primary cultures from mouse cornea were compared with those of the adult and 10-day postnatal mouse cornea. Keywords = corneal stroma maturation keratocyte fibroblast myofibroblast TGF beta 1 Keywords: other
2004-10-27 | GSE1867 | GEO