Project description:Chemokines have been suggested to play a role during development of left ventricular failure, but little is known about their role during right ventricular (RV) remodeling and dysfunction. The first aim of this study was to identify chemokines which are regulated during RV pressure overload. We then hypothesized that these chemokines regulate SLRPs (small leucine-rich proteoglycans)
Project description:Chemokines have been suggested to play a role during development of left ventricular failure, but little is known about their role during right ventricular (RV) remodeling and dysfunction. The first aim of this study was to identify chemokines which are regulated during RV pressure overload. We then hypothesized that these chemokines regulate SLRPs (small leucine-rich proteoglycans) A microarray study was performed on 5 pulmonary banded and sham operated wildype mice.
Project description:Performed a transcriptome analysis of control right ventricle and right ventricle subject to pressure and volume overload and demonstrated significant enrichment of genes involved in fibrosis with downregulation of metabolism in late stages of disease.
Project description:We found that β-arrestin 1 -/- mice were more sensitive to hypoxia-induced pulmonary arterial hypertension with increased right ventricle hypertrophy and higher right ventricle systolic pressure, while β-arrestin 2 -/- mice developed right ventricle hypertrophy comparable to wild type mice. Moreover, β-arrestin 1 -/- mice had worse right ventricle function than wild type mice in response to chronic hypoxia, whereas β-arrestin 2 -/- mice relatively preserved right ventricle function compared to wild type mice. To investigate the molecular mechanisms responsible for the worse PAH in β-arrestin 1 -/- mice, we performed lung transcriptome analysis of wild type, β-arrestin 1 -/-, and β-arrestin 2 -/- mice using high-throughput RNA-seq.
Project description:TGF-beta levels are known to increase in the aqueous humor of eye cells in patients with glaucoma. Increase TGF-beta is assumed to have a biochemical impact on the trabecular meshwork, and an increase in extracellular matrix formation, which may be responsible for decrease outflow facility of the eye. This may increase extracellular pressure, causing glaucoma. TGF-beta 1 may be the cause of abnormal accumulation of extracellular matrices in trabecular meshwork of eyes with primary open angle glaucoma. Transforming growth factor (TGF)-beta2 regulates the expression of proteoglycans in aqueous humor from human glaucomatous eyes. To identify gene expression changes as a result of TGF-beta1 and 2 treatment of human trabecular meshwork cells. We expect to see a change in expression of the proteoglycans in HTM cells as a response to TGF-beta treatment. Human Trabecular Meswork cells in the eye were bathed by aqueous humor. TM cells were removed from individuals with the following ages: 16,66,67,73, and 76. Each individual was treated with EtOH (control), TGF-beta1, or TGF-beta2. Total RNA from each individual was pooled for each chip. Technical replicates were created for each treatment type, for a total of 6 chips.
Project description:Transcriptional changes of the extracellular matrix in chronic thromboembolic pulmonary hypertension governs right ventricle remodeling and recovery
Project description:Proteoglycans are distributed in all animal tissues and play critical, multifaceted, physiological roles. Expressed in a spatially- and temporally-regulated manner, these molecules regulate interactions among growth factors and cell surface receptors and play key roles in basement membranes and other extracellular matrices. Due to the high degree of glycosylation by glycosaminoglycan (GAG), N-glycan and mucin-type O-glycan classes, the peptide sequence coverage of complex proteoglycans is revealed poorly by standard mass spectrometry-based proteomics methods. As a result, there is little information concerning how proteoglycan site specific glycosylation changes during normal and pathological processes. Here, we developed a workflow to improve sequence coverage and identification of glycosylated peptides in proteoglycans. We applied this workflow to the small leucine-rich proteoglycan decorin and the hyalectan proteoglycans; neurocan, brevican, and aggrecan.
Project description:Global gene expression analysis in PKCα-/- mouse skin reveals structural changes in the dermis and defective wound granulation tissue. The skin's mechanical integrity is maintained by an organised and robust dermal extracellular matrix (ECM). Resistance to mechanical disruption hinges primarily on homeostasis of the dermal collagen fibril architecture which is regulated, at least in part, by members of the small leucine-rich proteoglycan (SLRP) family. This array study presents data linking protein kinase C alpha (PKCα) to the regulated expression of multiple ECM components including SLRPs.
