Project description:For this project N-glycosylated peptides were extracted from tissue of a mouse model for ovarian cancer tissue and matched control mice. The extracted N-glycosites were analyzed by LC-MSMS
Project description:Thoracic aortic aneurysms and dissections (TAAD), as occur in Marfan syndrome (MFS), currently lack a cure. Our previous studies revealed that overactivation of the AKT-NO signaling pathway mediates aortic disease in MFS. However, the mechanisms upstream of AKT activation remained poorly understood. Here we identify the Fibronectin-αVβ3-PI3K-PIP3-PDK1-ILK cascade as a critical mediator of AKT-NOS2 upregulation and aortic disease in MFS. We show that fibronectin (FN) accumulates in the walls of human and mouse MFS aortas. Disrupting FN multimerization inhibits AKT activation and NOS2 induction in vascular smooth muscle cells (VSMCs), prevents aortic contractility dysregulation, and reverses aortic dilation in MFS mice. Mechanistically, both human and mouse MFS aortas exhibit αVβ3 and ILK upregulation. Pharmacological inhibition of αVβ3, PI3K, PDK1, and ILK, or their recruitment to the plasma membrane by PIP3, prevents FN-induced AKT activation and NOS2 upregulation in VMSCs and aortic contractility dysregulation. Furthermore, ILK inhibition or aortic silencing reverses aortic disease, while its deletion in smooth muscle cells prevents aortic growth in MFS mice. These findings establish the most thoroughly characterized pathway implicated in MFS to date and suggest a causative role for the FN-αVβ3-PI3K-PIP3-PDK1-ILK-AKT-NOS2 cascade in human TAAD, highlighting its components as potential targets for therapeutic intervention.
Project description:For Mouse KPC cell secreted extracellular vesicle LC-MSMS, extracellular vesicles in Alkbh5-WT or Alkbh5-KO KPC cell culture medium were isolated by ultracentrifugation. The protein and its levels in extracellular vesicle were determined through LC-MSMS.
Project description:This study focuses on the comprehensive analysis of the proteome in db/db mice, a model of type 2 diabetes mellitus (T2DM), using liquid chromatography coupled with mass spectrometry (LC-MSMS). The aim is to identify and quantify proteins present in tissues and fluids of db/db mice, providing insights into the pathophysiology of T2DM, related complications, and potential therapeutic targets. The data generated will contribute to a better understanding of the molecular mechanisms underlying diabetes and its complications, and may aid in the development of new diagnostic tools and treatment strategies for diabetes management.
Project description:Analysis of gene expression in cerebellum of postnatal day 10 Lurcher (Lc +/-) mouse, compared to wild type littermate. Keywords: other
Project description:Thoracic aortic aneurysms have a higher prevalence in male patients compared to female patients. Marfan syndrome causes a hereditary form of TAA with dilation of the aortic root. Male patients with Marfan syndrome are more likely than women to have aortic dilation and dissection and mouse models of Marfan syndrome demonstrate larger aortic roots in males compared to females even after adjustment for body size. Similar sex disparities are present in patients and models of abdominal aortic aneurysms where estrogen has been demonstrated to attenuate aneurysm formation perhaps through anti-inflammatory mechanisms. In this study we demonstrate the effects of estrogen on aortic dilation and rupture in a Marfan mouse model and we investigate if these effects operate through suppression of complement components of the immune system.
Project description:Project description: In this study, we performed proteome analyses to identify the key molecules that participate in aged mouse models of MI and transverse aortic constriction (TAC), the latter of which mimics increased left ventricular afterload that in the clinical setting predominantly occurs owing to aortic stenosis or systemic hypertension. B11 represents the tissues of an aged MI mouse. B17 represents the tissues of an aged TAC mouse. B15 represents the tissues of an aged Sham mouse.
Project description:Project description: In this study, we performed proteome analyses to identify the key molecules that participate in aged mouse models of MI and transverse aortic constriction (TAC), the latter of which mimics increased left ventricular afterload that in the clinical setting predominantly occurs owing to aortic stenosis or systemic hypertension. B11 represents the tissues of an aged MI mouse. B17 represents the tissues of an aged TAC mouse. B15 represents the tissues of an aged Sham mouse.