Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion of cells to components of the extracellular matrix has been shown to be critical in normal lung development, particularly during the pseudoglandular stage, when conducting airways are forming through a process of branching morphogenesis. Expression of factors that inhibit cellular adhesion might also modulate branching morphogenesis. SPARC is a secreted glycoprotein that exhibits antiadhesive effects on cultured cells and is widely expressed in embryonic tissues. In this report, we examine the distribution of SPARC in fetal rat lung during development and its effect on the process of branching morphogenesis. Immunohistochemistry and in situ hybridization studies revealed that SPARC was present in the airway epithelial cells during the pseudoglandular stage of lung development, and in blood vessels and smooth muscle cells associated with airways during the canalicular and saccular stages of development. We used an in vitro model of rat lung branching morphogenesis to examine airway branching in the presence of: a) a neutralizing anti-SPARC antibody; or b) a synthetic peptide from a region of SPARC that, like the native protein, perturbs cell adhesion and diminishes the synthesis of fibronectin and thrombospondin 1. Lungs cultured in the presence of either reagent exhibited diminished branching and an abnormal morphology that was characterized in part by dilated airways. These findings implicate SPARC in the development of the airways.
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PMID:SPARC participates in the branching morphogenesis of developing fetal rat lung. 765 84

Heparin-binding forms of vitronectin, a multifunctional adhesive glycoprotein, are associated with the extracellular matrix (ECM) at different locations in the body and serve to promote cell adhesion and the regulation of pericellular proteolysis at sites of angiogenesis. In the present study we characterized the interactions of vitronectin with the counter-adhesive protein osteonectin (also termed SPARC or BM40). Osteonectin and vitronectin were both found associated with the ECM of cultured endothelial cells and were localized in vessel wall sections of kidney tissue. In vitro, the heparin-binding multimeric isoform of vitronectin bound to immobilized osteonectin in a saturable manner with half-maximal binding at 30-40 nM. Preincubation of plasma vitronectin with plasminogen activator inhibitor 1 (PAI-1), which provoked multimer formation, induced the binding of vitronectin to osteonectin. Binding was optimal at physiological ionic strength, and binary complexes were stabilized by tissue transglutaminase-mediated cross-linking. In a concentration-dependent fashion, PAI-1, CaCl2, heparin and heparan sulphate, but not other glycosaminoglycans, interfered with the binding of vitronectin to osteonectin. Using vitronectin-derived synthetic peptides as well as mutant forms of recombinant osteonectin, we found that the heparin-binding region of vitronectin interacted with the C-terminal region of osteonectin that contains a high-affinity Ca2+-binding site with counter-adhesive properties. Adhesion of cultured endothelial cells was partly abrogated by osteonectin and was correspondingly reversed by vitronectin in a concentration-dependent manner. These results indicate that specific interactions between vitronectin and osteonectin modulate cell adhesion and might thereby regulate endothelial cell function during angiogenesis.
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PMID:Differential modulation of cell adhesion by interaction between adhesive and counter-adhesive proteins: characterization of the binding of vitronectin to osteonectin (BM40, SPARC). 916 72

Adhesion is a process that can be divided into three separate stages: (1) cell attachment, (2) cell spreading, and (3) the formation of focal adhesions and stress fibers. With each stage the adhesive strength of the cell increases. De-adhesion can be defined as the process involving the transition of the cell from a strongly adherent state, characterized by focal adhesions and stress fibers, to a state of intermediate adherence, represented by a cell that is spread, but that lacks stress fibers terminating at adhesion plaques. We propose that this modification of the structural link between the actin cytoskeleton and the extracellular matrix results in a more malleable cellular state conducive for dynamic processes such as cytokinesis, mitogenesis, and motility. Anti-adhesive proteins, including thrombospondin, tenascin, and SPARC, rapidly signal de-adhesion, potentially mediating proliferation and migration during development and wound healing. Intracellular signaling molecules involved in the regulation of de-adhesion are only beginning to be identified. Interestingly, many of the same signaling proteins recognized to play important roles during the process of adhesion have also been found to act during de-adhesion. Characterization of the precise mechanisms by which these signals modulate adhesive structures and the cytoskeleton will further our understanding of the regulation of adhesive strength and its function in cellular physiology.
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PMID:Signaling of de-adhesion in cellular regulation and motility. 985 39