Il13-stimulation of human paSMCs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE15739 | GEO | 2010/04/17
SECONDARY ACCESSION(S): PRJNA116629
REPOSITORIES: GEO
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Project description:Idiopathic pulmonary arterial hypertension (IPAH) is characterized by medial hypertrophy due to pulmonary arterial smooth muscle cell (paSMC) hyperplasia. Interleukin (IL)-13 is a potent regulator of tissue fibrosis and remodelling, and its effects are dependent on the cell-type specific expression of the IL-13 receptor isotypes IL-4Rα, IL-13Rα1, and IL-13Rα2. In order to identify the possible mechanism how IL-13 can exert its antiproliferative effect on paSMC microarray analysis was performed. For this purpose paSMC were stimulated with IL-13(10ng/ml) for 2h and 6h, respectively and subjected to microarray analysis. Comparison of stimulated versus unstimulated cells. 3 biological replicates, 2 time points
2010-05-07 | E-GEOD-15739 | biostudies-arrayexpress
Project description:Bone morphogenetic proteins (BMP) inhibit proliferation and induce apoptosis in pulmonary artery smooth muscle cells (PASMC) from normal subjects. Dysfunction of BMP signaling due to mutations in and/or downregulation of BMP receptors has been implicated in idiopathic pulmonary arterial hypertension (IPAH). We examined whether BMP differentially regulates gene expression in PASMC from normal subjects and IPAH patients using the Affymetrix microarray analysis. BMP-2 treatment (200 nM for 24 hrs) altered expression levels of 6,206 genes in normal and IPAH PASMC. 1,063 of these genes were regulated oppositely by BMP-2: 523 genes were downregulated by BMP-2 in normal PASMC but upregulated in IPAH PASMC, whereas 540 genes were upregulated by BMP-2 in normal PASMC but downregulated in IPAH PASMC. The divergent effects of BMP-2 on gene expression profiles indicate that PASMC may undergo significant phenotypic changes in IPAH patients during development of the disease. The transition of the antiproliferative effect of BMP-2 in normal PASMC to its proliferative effect in IPAH patients is attributed potentially to its differential effect on expression patterns of various genes that are involved in cell proliferation and apoptosis. Among the 6206 BMP-2-sensitive genes, there are more than 1800 genes whose expression levels were negatively (with a correlation coefficient, r, < -0.9) or positively (with r > +0.9) correlated with the pulmonary arterial pressure. These results suggest that BMP-mediated gene regulation is significantly altered in PASMC from IPAH patients and mRNA expression changes in BMP-regulated genes may be involved in the development of IPAH.
2007-09-07 | E-GEOD-2559 | biostudies-arrayexpress
Project description:Bone morphogenetic proteins (BMP) inhibit proliferation and induce apoptosis in pulmonary artery smooth muscle cells (PASMC) from normal subjects. Dysfunction of BMP signaling due to mutations in and/or downregulation of BMP receptors has been implicated in idiopathic pulmonary arterial hypertension (IPAH). We examined whether BMP differentially regulates gene expression in PASMC from normal subjects and IPAH patients using the Affymetrix microarray analysis. BMP-2 treatment (200 nM for 24 hrs) altered expression levels of 6,206 genes in normal and IPAH PASMC. 1,063 of these genes were regulated oppositely by BMP-2: 523 genes were downregulated by BMP-2 in normal PASMC but upregulated in IPAH PASMC, whereas 540 genes were upregulated by BMP-2 in normal PASMC but downregulated in IPAH PASMC. The divergent effects of BMP-2 on gene expression profiles indicate that PASMC may undergo significant phenotypic changes in IPAH patients during development of the disease. The transition of the antiproliferative effect of BMP-2 in normal PASMC to its proliferative effect in IPAH patients is attributed potentially to its differential effect on expression patterns of various genes that are involved in cell proliferation and apoptosis. Among the 6206 BMP-2-sensitive genes, there are more than 1800 genes whose expression levels were negatively (with a correlation coefficient, r, < –0.9) or positively (with r > +0.9) correlated with the pulmonary arterial pressure. These results suggest that BMP-mediated gene regulation is significantly altered in PASMC from IPAH patients and mRNA expression changes in BMP-regulated genes may be involved in the development of IPAH. Keywords = bone morphogenetic receptor protein Keywords = idiopathic pulmonary arterial hypertension Keywords = transcription factor Keywords = gene expression profile Keywords: other
2005-10-21 | GSE2559 | GEO
Project description:As the critical step of pathogenesis during hypoxic pulmonary arterial hypertension (PAH) vascular remodeling is closely associated with pulmonary arterial smooth muscle cell (PASMC) alterations induced by hypoxia that include persistent vasoconstriction, abnormal proliferation and PASMC resistance to apoptosis. Quercetin is a flavonoid compound extracted from green plants that inhibits proliferation, induces apoptosis, arrests the cell cycle, and rescues the constriction of PASMCs, but the underlying mechanisms remain poorly understood. In this study, we used a commercial Agilent Whole Rat Genome Oligo Microarray to determine the overall transcriptional response of PASMCs in response to exposure to hypoxia and the optimal concentration of quercetin. Hypoxia induced the upregulation of 1694 genes and the downregulation of 2091 genes compared with the normoxia group. Quercetin treatment resulted in 1790 upregulated genes and 1450 downregulated genes. Quercetin is known to cause differential expression of several of these genes that are known to promote proliferation, induce apoptosis (Cycs, Ppp3ca, Prkar2b, Akt3, Ppp3cc, Il1rap, Ntrk1), arrest the cell cycle (Chek2, Cdkn1c, Gadd45b, Stag2, Anapc7, Orc1, Ccne1, Myc3, Skp1, Espl1, Cdc45, Mcm4), and rescue PASMC constriction (Ramp1, Ramp3, Adcy5, Gnas, Prkcd, Itpr3, Adra1d, Calm1, Npr1, Avpr1a, Ednra, Adcy8). Real-time quantitative RT-PCR was performed to verify the microarray results. In conclusion, quercetin altered the expression profile of many genes regulated by hypoxia in PASMCs, which helps to further explore the mechanism of the effects of quercetin treatment on hypoxic PAH.
2015-08-20 | GSE72181 | GEO
Project description:Uncontrolled accumulation of pulmonary artery smooth muscle cells (PASMC) to the distal pulmonary arterioles (PAs) is one of the major characteristics of pulmonary hypertension (PH). Cellular senescence contributes to aging and lung diseases associated with PH and links to PH progression. However, the mechanism by which cellular senescence controls vascular remodeling in PH is not fully understood. The levels of senescence marker, p16INK4A and senescence-associated β-galactosidase (SA-β-gal) activity are higher in PA endothelial cells (ECs) isolated from idiopathic pulmonary arterial hypertension (IPAH) patients compared to those from healthy individuals. Hypoxia-induced accumulation of α-smooth muscle actin (αSMA)-positive cells to the PAs is attenuated in p16fl/fl-Cdh5(PAC)-CreERT2 (p16iΔEC) mice after tamoxifen induction. We have reported that endothelial TWIST1 mediates hypoxia-induced vascular remodeling by increasing platelet-derived growth factor (PDGFB) expression. Transcriptomic analyses of IPAH patient or hypoxia-induced mouse lung ECs reveal the alteration of senescence-related gene expression and their interaction with TWIST1. Knockdown of p16INK4A attenuates the expression of PDGFB and TWIST1 in IPAH patient PAECs or hypoxia-treated mouse lungs and suppresses accumulation of αSMA–positive cells to the supplemented ECs in the gel implanted on the mouse lungs. Hypoxia-treated mouse lung EC-derived exosomes stimulate DNA synthesis and migration of PASMCs in vitro and in the gel implanted on the mouse lungs, while p16iΔEC mouse lung EC-derived exosomes inhibit the effects. These results suggest that endothelial senescence controls αSMA–positive cell proliferation and migration in PH through TWIST1-PDGFB signaling.
2022-10-15 | PXD033549 | Pride
Project description:Idiopathic pulmonary arterial hypertension (iPAH) is a fatal disease that is associated with increased vascular resistance due to sustained contraction and enhanced proliferation of pulmonary vascular cells. The current treatment however is still not satisfactory. A better understanding of the involved molecular mechanisms may lead to new therapeutical strategies. Pulmonary arterial walls of healthy human lung tissue and of iPAH lungs were laser-microdissected. The extracted RNA was pooled and subjected to SMART-based RNA preamplification and fluorescence labeling. Gene expressions between iPAH and donors were compared using dual-channel microarrays. Keywords: disease characterization
2008-11-21 | GSE10704 | GEO
Project description:IPAH (Idiopathic Pulmonary Arterial Hypertension) Metagenome
| PRJNA279445 | ENA
Project description:We performed RNA-seq to analyze gene expression in human PASMCs (Pulmonary arterial smooth muscle cells) isolated from subjects without disease and from subjects with IPAH (idiopathic pulmonary hypertension)
2020-07-15 | GSE144274 | GEO
Project description:Pulmonary arterial hypertension (PAH) is characterized by severe obstruction of small pulmonary arteries and concomitant high pulmonary arterial pressure, resulting in progressive right ventricular failure. Previously, we demonstrated that long-term interleukin (IL)-33 administration in mice induced severe occlusive arterial hypertrophy in the lung, which was mediated by group 2 innate lymphoid cells (ILC2s). In response to IL-33, ILC2s accumulated around blood vessels and produced IL-5, leading to perivascular eosinophil recruitment. In this study, we further characterized IL-33-induced pulmonary arterial hypertrophy. We first demonstrated that long-term IL-33 administration caused an increase in the right ventricular pressure. In IL-33 deficient mice, pulmonary arterial hypertrophy mediated by eggs of Schistosoma mansoni (S. mansoni) was attenuated, accompanied with partial reduction in ILC2s, eosinophils and CD4+ T cells. In addition, proteomic analysis revealed dramatic changes in urine samples from mice treated with IL-33 or S. mansoni eggs. Resistin like alpha (RELM), a pulmonary hypertension-related molecule, in the urine was commonly detected in both treatments. Large amounts of RELM were observed in the lung from IL-33-treated mice. These observations support that IL-33-induced pulmonary arterial hypertrophy is a useful model to study the mechanism underlying development of PAH and expolar biomarkers to indicate the onset of PAH.
2024-09-27 | PXD055773 | JPOST Repository
Project description:Objective: Pulmonary complications in systemic sclerosis (SSc), including pulmonary fibrosis (PF) and pulmonary arterial hypertension (PAH), are the leading cause of mortality. We compared the molecular fingerprint of SSc lung tissues and matching primary lung fibroblasts to those of normal donors, and patients with idiopathic pulmonary fibrosis (IPF) and idiopathic pulmonary arterial hypertension (IPAH). Methods: Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively. Results: We identified a consensus of 242 and 335 genes that were differentially expressed in lungs and primary fibroblasts, respectively. Enriched function groups in SSc-PF and IPF lungs included fibrosis, insulin-like growth factor signaling and caveolin-mediated endocytosis. Functional groups shared by SSc-PAH and IPAH lungs included antigen presentation, chemokine activity, and IL-17 signaling. Conclusion: Using microarray analysis on carefully phenotyped SSc and comparator lung tissues, we demonstrated distinct molecular profiles in tissues and fibroblasts of patients with SSc-associated lung disease compared to idiopathic forms of lung disease. Unique molecular signatures were generated that are disease- (SSc) and phenotype- (PF vs PAH) specific. These signatures provide new insights into pathogenesis and potential therapeutic targets for SSc lung disease. Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively.
2013-06-21 | E-GEOD-48149 | biostudies-arrayexpress