Biomedical subjects

W Scott Argraves

Publications and source records attributed to W Scott Argraves.

27 records · Page 2Linked to original sources

PubMed2003

The MUSC DNA Microarray Database.

SUMMARY: The Medical University of South Carolina (MUSC) DNA Microarray Database is a web-accessible archive of DNA microarray data. The database was developed using the DNA microarray project/data management system, micro ArrayDB. Annotations for each DNA microarray project and associated cRNA target information are stored in a MySQL relational database and linked to array hybridization data (raw and normalized). At the discretion of investigators, data are placed into the public domain where they can be interrogated and downloaded through a web browser. In addition to serving as an online resource of gene expression data, the MUSC DNA Microarray Database is a model for other academic DNA microarray data repositories. AVAILABILITY: Browsing and downloading of MUSC DNA Microarray Database information can be done after registration at http://proteogenomics.musc.edu/pss/home.php.

Academic Medical Centers↗

PubMed2003

Megalin and the neurodevelopmental biology of sonic hedgehog and retinol.

Megalin is a receptor expressed by embryonic epithelia that mediates endocytosis of numerous ligands, including sonic hedgehog (Shh) and retinol, the precursor to retinoic acid (RA). The importance of Shh and RA signaling in neurodevelopment, combined with the fact that megalin-deficient mice show profound neurodevelopmental abnormalities, has raised questions as to the possible role of megalin in Shh and RA signaling. Several mechanisms could explain how megalin influences Shh and RA signaling in the context of neurodevelopment. These include the involvement of megalin in the transport of Shh and retinol within neuroepithelia, as well as direct signal transduction as a response to binding of Shh and retinol to megalin.

Animals↗

PubMed2003

Patterning of embryonic blood vessels.

Morphometric methods were developed to characterize the geometry of vascular patterns in avian and murine embryos. By using these methods, we found that networks of blood vessels formed during vasculogenesis share similar geometric properties (i.e., mean blood vessel diameters and avascular space diameters) regardless of developmental stage, location, or species in which they form. We also found that endothelial cell density within a unit area of an embryonic vasculature could be used to accurately distinguish between a small diameter, capillary-like vascular network (low endothelial cell density) and a large diameter, presinusoidal network (high endothelial cell density). Furthermore, we show that endothelial cell size remains constant in small and large diameter vessels, indicating that increased endothelial cell size is not the basis for diversity in vessel diameter. These observations serve as a foundation for future studies seeking to evaluate the effects of agents or genetic mutations on aspects of vasculogenesis.

Allantois↗

PubMed2003

Co-expression and interaction of cubilin and megalin in the adult male rat reproductive system.

Cubilin is a peripheral membrane protein that cooperates with the endocytic receptor megalin to mediate endocytosis of ligands in various polarized epithelia. Megalin is expressed in the male reproductive tract where it has been implicated in the process of sperm membrane remodeling. A potential role for cubilin in the male reproductive tract has not been explored. Using RT-PCR, we found that cubilin and megalin mRNAs are expressed in the efferent ducts, corpus and cauda epididymis, and proximal and distal vas deferens. Immunohistological analysis revealed that cubilin was expressed in nonciliated cells of the efferent ducts, principal cells of the corpus and cauda epididymis and vas deferens. Immunogold EM showed cubilin in endocytic pits, endocytic vesicles, and endosomes of these cells. The expression profile of cubilin in the male reproductive tract was coincident with that of megalin except in principal cells of the caput epididymis. Double immunogold labeling showed that cubilin and megalin co-localized within the endocytic apparatus and recycling vesicles of efferent duct cells. Neither protein was found in lysosomes. Injection of RAP, an antagonist of megalin interaction with cubilin, reduced the level of intracellular cubilin in cells of the efferent ducts and vas deferens. In conclusion, cubilin and megalin are co-expressed in cells of the epididymis and vas deferens and the endocytosis of cubilin in these tissues is dependent on megalin. Together, these findings highlight the potential for a joint endocytic role for cubilin and megalin in the male reproductive tract.

Animals↗

PubMed2003

Fibulins: physiological and disease perspectives.

The fibulins are a family of proteins that are associated with basement membranes and elastic extracellular matrix fibres. This review summarizes findings from studies of animal models of fibulin deficiency, human fibulin gene mutations, human tumours and injury models that have advanced our understanding of the normal and pathological roles of members of this formerly obscure family.

Amino Acid Sequence↗

PubMed2003

Transplanted human cord blood cells give rise to hepatocytes in engrafted mice.

Recent studies suggest that rodent hepatocytes may be derived from hematopoietic stem cells. In the current study, the potential hematopoietic origin of hepatocytes was addressed using xenogeneic transplantation of human cord blood cells. CD34(+) or CD45(+) human cord blood cells were transplanted into "conditioned" newborn NOD/SCID/beta2-microglobulin(null) mice. At 4 to 5 months post-transplantation, livers of the recipient mice were cryosectioned and examined for evidence of human hepatocyte engraftment using RT-PCR to detect human albumin mRNA, immunohistochemistry to detect human hepatocytic proteins, and fluorescence in situ hybridization (FISH) to detect the presence of human centromeric DNA. Analysis of the bone marrow of transplanted mice revealed that 21.0-45.9% of the cells were human CD45(+) cells. FISH analysis of frozen sections of transplanted mouse liver revealed the presence of engrafted cells positive for human centromeric DNA. That engrafted human cells functioned as hepatocytes was indicated by the expression of human albumin mRNA, as judged by RT-PCR. FISH analysis with human and mouse centromeric DNA probes excluded spontaneous cell fusion as the cause for the generation of human hepatocytes. Human cord blood cells can give rise to hepatocytes in a xenogeneic transplantation model. This model will be useful to further characterize the cord blood progenitors of hepatocytes.

Animals↗

PubMed2002

Megalin functions as an endocytic sonic hedgehog receptor.

Embryos deficient in the morphogen Sonic hedgehog (Shh) or the endocytic receptor megalin exhibit common neurodevelopmental abnormalities. Therefore, we have investigated the possibility that a functional relationship exists between the two proteins. During embryonic development, megalin was found to be expressed along the apical surfaces of neuroepithelial cells and was coexpressed with Shh in the ventral floor plate of the neural tube. Using enzyme-linked immunosorbent assay, homologous ligand displacement, and surface plasmon resonance techniques, it was found that the amino-terminal fragment of Shh (N-Shh) bound to megalin with high affinity. Megalin-expressing cells internalized N-Shh through a mechanism that was inhibited by antagonists of megalin, viz. anti-receptor-associated protein and anti-megalin antibodies. Heparin also inhibited N-Shh endocytosis, implicating proteoglycans in the internalization process, as has been described for other megalin ligands. Use of chloroquine to inhibit lysosomal proteinase activity showed that N-Shh endocytosed via megalin was not efficiently targeted to the lysosomes for degradation. The ability of megalin-internalized N-Shh to bypass lysosomes may relate to the finding that the interaction between N-Shh and megalin was resistant to dissociation with low pH. Together, these findings show that megalin is an efficient endocytic receptor for N-Shh. Furthermore, they implicate megalin as a new regulatory component of the Shh signaling pathway.

Animals↗

PubMed2002

VEGF signaling is required for the assembly but not the maintenance of embryonic blood vessels.

Here we investigated the importance of vascular endothelial growth factor (VEGF) signaling to the de novo formation of embryonic blood vessels, vasculogenesis, as opposed to the maintenance of blood vessels. We found that antagonizing the activity of the VEGF signaling pathway by using soluble VEGF receptor 1 (sFlt1) or VEGF antibodies inhibited vasculogenesis that occurs in embryos and in cultures of 7.5 days postcoitus prevascular mesoderm. Antagonist treatment resulted in the formation of clusters of endothelial cells not normally observed during vasculogenesis. In contrast, when embryos with established vasculatures or cultures of vascularized mesoderm were treated with sFlt1 or VEGF antibodies, no discernible alterations to the preexisting blood vessels were observed. These observations indicate that, although VEGF signaling is required to promote the mesenchymal to epithelial transition by which angioblasts assemble into nascent endothelial tubes, it is not required by endothelial cells to maintain their organization as an endothelium.

Allantois↗

PubMed2002

Diverse roles for the LDL receptor family.

The low-density lipoprotein (LDL) receptor family consists of several related scavenger receptors that not only function as important cargo transporters, but also inform the cell of changes in its environment by mediating signaling responses. The LDL receptor was the first family member to be characterized and its function seems to be restricted to lipoprotein metabolism. By contrast, lipoprotein metabolism does not appear to be the exclusive function of the other characterized LDL receptor family members. It is now apparent that cargo transport by members of the LDL receptor family is closely associated with regulation of cellular physiology and cellular signaling events. Here, we focus on the diverse biological activities of certain members of this family.

Animals↗