Project description:We report the application of RNA sequencing in lung tissues of MCT rats, that were treated with Angiotensin 2 or TRV023 or Losartan to study their effects on Pulmonary hypertension. We received FPKM data of each gene from each group of MCT rats. The gene expression of the study MCT rats were normalized to control MCT rat. The differentially expressed genes in Angiotensin 2 and TRV023 treated MCT rats, confirmed that like Angiotensin 2, TRV023 is also involved in vascular remodelling and lead to worsening of pulmonary hypertension.
Project description:TMT-based quantitative proteomics was performed on lung tissues derived from SD rats which were treated with monocrotaline (MCT) for 1to 4 weeks. Similar analysis was performed with RV tissues from rats treated with MCT for 3 weeks. In addition, phosphoproteomic analysis was performed with lung and RV from rats treated with MCT for 3 weeks.
Project description:We performed molecular phenotyping of RV remodeling, using transcriptome analysis of RV tissue obtained from MCT-induced rats (of both male and female animals). The clustering approach along with precise hemodynamics assessments identified “early" and "late" subgroups of decompensated state in rat RV. Further molecular characterization of these subgroups identified distinct molecular genes and pathways within different stages of RV remodeling. This study provided a resource to comprehensively compare human RV remodeling with the current animal model of PH (MCT), and led to validation of state-specific biomarkers and potential therapeutic targets for RV dysfunction.
Project description:To investigate the underlying mechanism of pulmonary hypertension, the model of monocrotaline (MCT)-treated pulmonary arterial hypertension (PAH) rats were constructed to detect the differentially expressed profile of circRNAs in lung tissue of PAH rat. The whole genome microarray expression profiling analysis as a discovery platform have been employed to identify genes difference.
Project description:MCT-1 is an oncogene initially identified in a human T-cell lymphoma. Subsequently, MCT-1 protein levels were found to be elevated in a subset of diffuse large B-cell lymphoma. Forced expression of MCT-1 has recently been shown to induce cell proliferation as well as activate survival-related pathways protecting lymphoid cells from apoptosis. We document here that MCT-1 interacts with the density-regulated protein (DENR/DRP), containing the SUI1 translation initiation domain, found in many translation initiation factors. MCT-1 contains the PUA domain, a recently described RNA binding domain that is found in several tRNA and rRNA modification enzymes. Our findings established that MCT-1 protein is interacting with the cap complex through its PUA domain and enhances translation. Furtheremore, our data support a putative role for the MCT-1 oncogene in translation and suggests a mechanism for its role in lymphomagenesis. Keywords: Gene upregulation by MCT-1
Project description:Rats (Wag/Rij, females) were chronically treated with Losartan (20mg/d), an angiotensin II-receptor blocker during 9 months. Gene expression profiling was performed on aortic media to understand the long-term effect of this molecule on the cardiovascular system. Two-conditions experiment, Ctrl vs Losartan-treated animals. Biological replicates: 5 control replicates, 5 Losrtan-treated animals. All the RNA samples were pooled to provide a reference RNA for a two-color experiment.
Project description:Chronic kidney disease (CKD) is one of the major global health problems with high incidence, poor prognosis and high medical cost. However, few pharmacological options are available for CKD. Metformin is widely used for treatment of type-2 diabetes, but recent works showed that metformin ameliorates tumor progression, inflammatory disease and tissue fibrosis. Whether metformin ameliorates non-diabetic chronic glomerular disease and CKD is unexplored. Here we showed that metformin or losartan (used as control) has protective effects against CKD by suppressing proteinuria, renal inflammation, fibrosis and glomerular injury in Alport syndrome mouse model, which spontaneously manifests chronic glomerular and kidney disease. Transcriptome analysis showed that metformin and losartan influenced molecular pathways of metabolism and inflammation, respectively. While metformin specifically affected genes that were classified as metabolic regulators, losartan specifically altered genes that were classified as inflammatory regulators. Metformin also induced multiple signaling pathways not affected by losartan. Overall, metformin ameliorates non-diabetic chronic glomerular diseases, and could be considered a therapeutic option for CKD. We used microarrays to investigate the global gene expression underlying the protective effects of metformin on Alport syndrome mice model
Project description:In order to obtain a global perspective of the effect of EHP-101 and Losartan on cardiac fibrosis, we performed a mRNA-Seq analysis of the myocardial tissue changes in response to Ang II, Ang II + EHP-101 and Ang II + Losartan.
Project description:Rats (Wag/Rij, females) were chronically treated with Losartan (20mg/d), an angiotensin II-receptor blocker during 9 months. Gene expression profiling was performed on aortic media to understand the long-term effect of this molecule on the cardiovascular system.
Project description:PAH was induced by 60mg/kg MCT and an aorto-caval shunt. At different timepoints of PAH progression (day 14, 21 and 28 after MCT-injection), the left lung with PAH was hemodynamically unloading by unilateral orthotopic transplatation into a syngeneic, healthy recipient. All day 14 and 7/10 day 21 transplanted lungs showed reversal of PAH after LTx. All day 28 and 3/10 day 21 transplanted lungs showed PAH progression after LTx. Lung tissue of Reversible and Irreversible PAH and normal controls, acquired at LTx, was compared using RNA-seq.