The Roles of the Notch2 and Notch3 Receptors in Vascular Smooth Muscle Cells - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook The Roles of the Notch2 and Notch3 Receptors in Vascular Smooth Muscle Cells write by Jeremy Todd Baeten. This book was released on 2016. The Roles of the Notch2 and Notch3 Receptors in Vascular Smooth Muscle Cells available in PDF, EPUB and Kindle. The Notch signaling pathway has long been intricately linked with the development and function of the vasculature. In vascular smooth muscle cells (VSMCs), Notch signaling has a great influence on phenotype and is a strong promoter of differentiation and expression of contractile genes necessary to produce a functional vessel wall. However, the role of Notch signaling in VSMC proliferation and survival is less well defined, and some cases contradictory reports are given. Also, the contributions of each individual Notch receptor have not been clearly described. Thus, to better understand Notch signaling in VSMC phenotype, we investigated the specific roles of the predominant Notch receptors in VSMCs as they relate to differentiation, proliferation, and survival. We found that Notch3 promotes Platelet-Derived Growth Factor (PDGF)-induced proliferation in VSMCs, while Notch2 inhibits it. We also found that Notch3 was able to promote cell survival in response to apoptosis cues, while Notch2 had no discernible effect. Interestingly, we also found the expression of Notch2 and Notch3 were changed in response to proliferation and apoptosis inducers. Notch2 mRNA was significantly decreased after PDGF-BB treatment, a proliferation inducer, and Notch3 protein was degraded rapidly in response to induction of apoptosis. Additionally, we demonstrated that Notch3’s induction of cell survival genes required MEK/ERK signaling and Notch3 was capable of increasing levels of phosphorylated ERK. Altogether, these findings demonstrate that Notch2 and Notch3 have unique functions in regulating VSMC phenotype. In a mouse model devoid of Notch2 and Notch3 in smooth muscle cells, we were able to show that Notch2 and Notch3 are required for normal closure of the ductus arteriosus. Animals without Notch2 in VSMCs presented with patent ductus arteriosus with increasing incidence combined with the loss of Notch3. These mice died within one day of birth and also presented with aortic dilation. These phenotypes wee correlated with a significant loss of the smooth muscle contractile genes MYH11 and ACTA2, and it has been previously reported that defects in contractile differentiation can produce the PDA phenotype. This suggests that the Notch2 and Notch3 share an overlapping role in promoting VSMC differentiation. The Notch-regulated microRNA 145 has been strongly implicated in VSMC differentiation and also recently shown to regulate cardiovascular fibrosis. In order to better understand these connections to differentiation and fibrosis, we created and characterized a transgenic mouse for conditional expression of miR145, miR145TG. We were able to select a line that faithfully expresses the transgene and produces mature miR145 transcript. This model will allow for further investigation into miR145’s roles in promoting VSMC differentiation and mediating fibrosis.
Endothelial Cell-dependent Notch Signaling Regulates Vascular Smooth Muscle Cell Phenotypes
Endothelial Cell-dependent Notch Signaling Regulates Vascular Smooth Muscle Cell Phenotypes - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Endothelial Cell-dependent Notch Signaling Regulates Vascular Smooth Muscle Cell Phenotypes write by Cho-Hao Lin. This book was released on 2015. Endothelial Cell-dependent Notch Signaling Regulates Vascular Smooth Muscle Cell Phenotypes available in PDF, EPUB and Kindle. Endothelial cell-dependent Notch signaling plays many critical roles in homeostasis and remodeling in the vasculature and serves an important role in the communication between endothelial cells and mural cells, including vascular smooth muscle cells (SMCs), pericytes, and fibroblasts. Our lab previously showed that endothelial cells govern SMC function and promote smooth muscle differentiation. Endothelial cells are able to induce smooth muscle cells into a mature contractile phenotype through cell contact and Notch signaling. Furthermore, Notch signaling has been shown to regulate SMC-specific gene and miR-143/145 expression to govern SMC differentiation. In this study, I demonstrated that endothelial cell-dependent Notch signaling enhances both contractile and synthetic phenotypes in smooth muscle cells, suggesting endothelial cells not only increase the contractile ability of smooth muscle cells, but might also signal to smooth muscle cells to build the basement membrane and form a functional blood vessel. My data indicate that the Notch2 receptor has a unique function in the regulation of SMC proliferation, and the Notch3 receptor has a distinct role in the regulation of synthetic phenotypes in smooth muscle cells.
The Atlas of Mouse Development
The Atlas of Mouse Development - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook The Atlas of Mouse Development write by Matthew H. Kaufman. This book was released on 1992-09. The Atlas of Mouse Development available in PDF, EPUB and Kindle. Not since the early 1970s has there been an attempt to describe and illustrate the anatomy of the developing mouse embryo. More than ever such material is needed by biologists as they begin to unravel the molecular mechanisms underlying development and differentiation. After more than ten years of painstaking work, Matt Kaufman has completed The Atlas of Mouse Development--the definitive account of mouse embryology and development. For all those researching or studying mammalian development, The Atlas of Mouse Development will be the standard reference work for many years to come. Provides a comprehensive sequential account of the development of the mouse from pre-implantation to term Contains clear and concise descriptions of the anatomical features relevant to each stage of development Large format for easy use Contains explanatory notes and legends, and more than 180 meticulously labeled plates, 1,300 photographs of individual histological sections, and 200 electron micrographs, illustrating: Intermittent serial histological sections through embryos throughout embryogenesis and organogenesis Differentiation of specific organs and organ systems, including the spinal cord, eyes, gonads, kidneys, lungs and skeletal system External appearance of intact embryos throughout development
Molecular Mechanisms of Notch Signaling
Molecular Mechanisms of Notch Signaling - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Molecular Mechanisms of Notch Signaling write by Tilman Borggrefe. This book was released on 2018-07-20. Molecular Mechanisms of Notch Signaling available in PDF, EPUB and Kindle. This book describes the Notch signaling pathway with a focus on molecular mechanisms. The Notch signaling pathway is a seemingly simple pathway that does not involve any second messenger. Upon ligand binding two consecutive proteolytic cleavages of the NOTCH receptor release the Notch intracellular domain from the membrane. The Notch intracellular domain migrates into the nucleus and activates gene expression. Recently, new technologies allowed us to better understand this pivotal signaling cascade and revealed new regulatory mechanisms. The different chapters cover many aspects of the Notch signaling focusing on the mechanisms governing the receptor/ligand interaction as well as on the downstream intracellular signaling events. Aspects of both canonical and non-canonical signaling are discussed and the function of Notch signaling in physiological and pathological contexts are elucidated. This book is not only intended for experts but it should also be a useful resource for young, sprouting scientists or interested scientists from other research areas, who may use this book as a stimulating starting point for further discoveries and developments.
Pancreatic Cancer
Pancreatic Cancer - read free eBook in online reader or directly download on the web page. Select files or add your book in reader. Download and read online ebook Pancreatic Cancer write by Douglas B. Evans. This book was released on 2006-04-18. Pancreatic Cancer available in PDF, EPUB and Kindle. The MD Anderson Solid Tumor Oncology series presents cutting-edge surgical treatment and medical therapy for specific sites. This volume, Pancreatic Cancer, addresses epidemiology and molecular biology, inherited syndromes, staging, surgical techniques, multimodality therapy, and emerging therapies. The individual chapters focus on narrow, specific topics to produce a reference work of value to those interested in pancreatic cancer from a clinical and translational research perspective. A must-have for surgical oncologists and general surgeons.
