ScRNA-seq analysis of the livers from the endothelial cell-specific CTGF KO mice after pIVCL
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE305482 | GEO | 2026/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:We performed scRNA-seq analysis on the livers from the mice treated with a pan-integrin αV inhibitor, CWHM-12, after partial inferior vena cava ligation (pIVCL), a mouse model of congestive hepatopathy. The scRNA-seq analysis showed that integrin αV inhibition decreased the expression of YAP/TAZ target genes in pericentral LSECs and collagen expression in HSCs, caused by hepatic congestion.
2026-03-01 | GSE305630 | GEO
Project description:We performed scRNA-seq analysis on murin livers after partial inferior vena cava ligation (pIVCL), a mouse model of congestive hepatopathy. We identified connective tissue growth factor (CTGF) as one of the most upregulated genes in pericentral (zones 2 and 3) LSECs. The scRNA-seq analysis also showed that the integrin signaling pathway was activated and the expression of YAP/TAZ target genes was upregulated in pericentral LSECs.
2026-03-01 | GSE291326 | GEO
Project description:Background & Aims Congestion alters the microenvironment of the liver sinusoid along the portal-central axis. We studied spatial changes in immune cells in the sinusoid which contribute to congestive fibrosis and portal hypertension (PHTN). Methods To visualize the distribution of immune cells in congestive hepatopathy (CH), we performed imaging mass cytometry (IMC) on liver tissue from patients with CH, Fontan-associated liver disease (FALD), and controls. We performed partial ligation of the inferior vena cava (pIVCL) to simulate CH in mice and isolated primary liver cells for single cell RNA-sequencing (scRNA-seq) to study zonation of liver sinusoidal endothelial cells (LSECs). After pIVCL, mice were treated with intraperitoneal injections of AMG487, an inhibitor of the CXCL9 receptor. Results Peri-central macrophages are enriched in CH and FALD. Given the role of CXCL9 in macrophage patterning in the liver, we performed RNA in situ hybridization (RNAish) in CH and determined that CXCL9 was highly expressed in LSECs in FALD, suggesting that LSECs recruit macrophages in CH. After pIVCL, treatment with AMG487 attenuated portal pressures, fibrosis, and intra-hepatic macrophages. To study changes in LSECs which promote macrophage chemotaxis, we performed scRNA-seq after pIVCL and sham procedures. Analysis revealed 3 LSEC subpopulations according to sinusoidal location. RNANish identified peri-central LSECs as the predominant source of CXCL9 in FALD. In vitro analyses revealed that -catenin and hypoxia inducible factor-1α regulate CXCL9 transcription in peri-central LSECs. Conclusions CXCL9 derived from peri-central LSECs enriches intra-hepatic macrophages in CH and FALD, contributing to congestive fibrosis and PHTN. Strategies to target LSEC-derived CXCL9 may prevent the progression of CH and FALD.
2024-01-27 | GSE253915 | GEO
Project description:We created a rat renal congestion model and investigated the effect of renal congestion on hemodynamics and molecular mechanisms. The inferior vena cava (IVC) between the renal veins was ligated by suture in male Sprague-Dawley rats to increase upstream IVC pressure and induce congestion in the left kidney only. Left kidney congestion reduced renal blood flow, glomerular filtration rate, and increased renal interstitial hydrostatic pressure. Tubulointerstitial and glomerular injury and medullary thick ascending limb hypoxia were observed only in the congestive kidneys. Molecules related to extracellular matrix expansion, tubular injury, and focal adhesion were upregulated in microarray analysis. Renal decapsulation ameliorated the tubulointerstitial injury. Electron microscopy captured pericyte detachment in the congestive kidneys. Transgelin and platelet-derived growth factor receptors, as indicators of pericyte-myofibroblast transition, were upregulated in the pericytes and the adjacent interstitium. With the compression of the peritubular capillaries and tubules, hypoxia and physical stress induce pericyte detachment, which could result in extracellular matrix expansion and tubular injury in renal congestion.
2018-11-14 | GSE114031 | GEO
Project description:The number of heart failure (HF) patients is increasing. HF is frequently accompanied by kidney dysfunction and such organ failure is closely related. Recent investigations revealed that increased renal venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in HF patients; however, the underlying responsible mechanisms are unknown. We demonstrated that reduced blood flow speed in peritubular capillaries (PTCs) by renal congestion and upregulation of nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral renal congestion by coarctation of the inferior vena cava between renal veins. Intravital imaging highlighted the notable dilatation of PTCs and decreased renal blood flow speed in the congestive kidney. Renal damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes (PMNs) within PTCs was observed at the acute phase after injury. Pharmacological inhibition of NF-κB ameliorated renal congestion-mediated exacerbation of kidney injury. In vitro, adhesion of PMNs on the TNFα-stimulated endothelial cells was accelerated by perfusion of PMNs at a slower speed, which was cancelled by the inhibition of NF-κB signaling. Our study demonstrates the importance of slower blood flow accompanying activated NF-κB signaling in the congestive kidney in the exacerbation of renal injury. These mechanisms may explain how increased renal venous pressure in HF patients causes the deterioration of kidney dysfunction. Inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased renal venous pressure.
2024-02-16 | GSE166838 | GEO
Project description:We performed scRNA-seq analysis on livers from the mouse model of CCl4-induced liver fibrosis. The scRNA-seq analysis showed that CTGF expression was increased only in zone 2 LSECs, and that YAP was not activated in any cluster of LSECs.
2026-03-01 | GSE305772 | GEO
Project description:A porcine microarray study of right ventricular failure due to coronary artery ligation of the right ventricular free wall and subsequent treatment of right ventricular failure by volume unloading using a shunt between superior vena cava and the pulmonary artery (Glenn-shunt) 1. Surgical preparation with a 12 mm graft between superior vena cava and pulmonary artery, the graft is then clamped - Baseline sample using a biopsy needle. 2. After surgical preparation the coronary arteries of the right ventricular free wall are ligated, then heart failure develops over 120 minutes - Failure sample using a biopsy needle. 3. The shunt is then opened and the superior vena cava closed between the shunt and right atrium, diverting the blood from superior vena cava through the shunt for a period of 15 minutes partially unloading the right ventricle - Shunt sample using a biopsy needle. A series of six pigs, three samples from each animal: baseline, failure and shunt/treatment.
2011-08-23 | E-GEOD-31619 | biostudies-arrayexpress
Project description:Arteries and veins modulate cardiovascular homeostasis and contribute to the pathogenesis of hypertension. Functional differences between normal arteries and veins are based upon differences in gene expression. To better characterize these expression patterns, and to identify candidate genes that could be manipulated selectively in the venous system, we performed whole genome expression profiling of rat arteries and veins using the CodeLink platform. We used the major artery and vein of the rat, the thoracic aorta and caudal vena cava, respectively. Expression of mRNA for thrombospondins (TSP-1, 2, 4) was greater than 5-fold higher in veins vs arteries. The most prominent gene expression difference between the normal aorta and vena cava was pancreatitis associated protein (PAP1), a protein with anti-inflammatory functions that was 64-fold higher in vena cava vs aorta. Higher mRNA expression of TSP-1, TSP-2, TSP-4 and PAP1 in vena cava vs aorta was confirmed with real time RT-PCR. Importantly, immunohistochemical analysis of blood vessels sections qualitatively confirmed a higher expression of proteins in vena cava vs aorta. These studies report a difference in inflammatory genes in arteries vs veins. A particularly notable finding is the discovery of PAP1 mRNA and protein expression in peripheral blood vessels with a substantially higher expression in the veins. Data from these studies may provide novel insights into the genetic basis for functional differences between arteries and veins in health and disease. Whole genome expression profiling of aorta and vena cava whole tissues from normal male Sprague-Dawley rats (6 biological replicates each) was performed using the CodeLink Rat Whole Genome Bioarrays.
2009-07-13 | E-GEOD-12255 | biostudies-arrayexpress
Project description:Deep vein thrombosis (DVT) is a common clinical problem, but its cellular and molecular mechanisms remain incompletely understood. We performed single-cell RNA sequencing (scRNA-seq) on the vein wall of mouse inferior vena cava (IVC) ligation model of deep vein thrombosis (DVT), to analyze the transcriptomic changes in the vein wall during acute venous thrombosis.
2023-02-10 | GSE221978 | GEO
Project description:Arteries and veins modulate cardiovascular homeostasis and contribute to the pathogenesis of hypertension. Functional differences between normal arteries and veins are based upon differences in gene expression. To better characterize these expression patterns, and to identify candidate genes that could be manipulated selectively in the venous system, we performed whole genome expression profiling of rat arteries and veins using the CodeLink platform. We used the major artery and vein of the rat, the thoracic aorta and caudal vena cava, respectively. Expression of mRNA for thrombospondins (TSP-1, 2, 4) was greater than 5-fold higher in veins vs arteries. The most prominent gene expression difference between the normal aorta and vena cava was pancreatitis associated protein (PAP1), a protein with anti-inflammatory functions that was 64-fold higher in vena cava vs aorta. Higher mRNA expression of TSP-1, TSP-2, TSP-4 and PAP1 in vena cava vs aorta was confirmed with real time RT-PCR. Importantly, immunohistochemical analysis of blood vessels sections qualitatively confirmed a higher expression of proteins in vena cava vs aorta. These studies report a difference in inflammatory genes in arteries vs veins. A particularly notable finding is the discovery of PAP1 mRNA and protein expression in peripheral blood vessels with a substantially higher expression in the veins. Data from these studies may provide novel insights into the genetic basis for functional differences between arteries and veins in health and disease.
2009-07-13 | GSE12255 | GEO