Fibrillin-1 regulates mesangial cell attachment, spreading, migration and proliferation

Abstract

The microfibrillar protein fibrillin-1 is present in many organs, including the vasculature, eye, and dermis, and is thought to convey structural anchorage and elastic strength. Fibrillin-1 is also a component of the mesangial matrix. To assess the functional relevance of fibrillin-1 for cell-matrix interactions in the glomerulus, we studied the attachment, spreading, migration and proliferation of mesangial cells on fibrillin-1 and the regulation of fibrillin-1 in experimental anti-Thy1.1 nephritis displaying mesangial cell migration and proliferation in vivo. During the acute phase of experimental Thy1.1 nephritis, glomerular fibrillin-1 messenger ribonucleic acid expression and protein immunoreactivity were significantly induced as compared to controls. In a hexosaminidase-based adhesion assay, mesangial cells showed concentration-dependent attachment to fibrillin-1, similar to what was observed for fibronectin. The cell attachment was Arg-Gly-Asp dependent. Further, fibrillin-1 significantly promoted spreading and focal contact formation detected by immunostaining for vinculin. Mesangial cell migration, assessed by a transmigration assay, and proliferation, measured by a 5-bromo-2'-deoxy-uridine incorporation assay, were augmented by fibrillin-1. In diabetic mice underexpressing fibrillin-1, glomerular cell proliferation, determined by counting proliferating cell nuclear antigen-positive cells in renal sections, was significantly lower than in diabetic control mice. We conclude that fibrillin-1 promotes mesangial cell attachment, spreading, migration, and proliferation. We speculate that fibrillin-1 may thus contribute to mesangial hypercellularity during glomerular disease.

Ultrastructural localization of fibrillin-1 and fibrillin-2 in oxytalan fibers in periodontal ligament of Japanese Macaca fuscata monkey

“…These data may constitute intriguing evidence for functional variation in oxytalan fibers in periodontal ligament. In recent in vitro studies, fibrillins influenced the adhesion, spread and migration of ligamentum nuchae fibroblasts, mesangial cells and lung fibroblasts via ArgGly-Asp (RGD) peptide-dependent integrins avb3 and a5b1 (Porst et al 2006;McGowan et al 2008). Therefore, it is assumed that oxytalan fibers formed by fibrillinmicrofibrils in periodontal ligament regulate the adhesion, spread, migration and proliferation of fibroblasts via integrins.…”

Myocilin promotes substrate adhesion, spreading and formation of focal contacts in podocytes and mesangial cells

“…Myocilin as a substrate for mesangial cell or podocyte attachment Recombinant myocilin was tested for its ability to mediate attachment of mesangial cells or podocytes relative to (Bijian et al 2005;Porst et al 2006). 96-well plates were coated overnight with each of the substrates and the remaining coating solution was analyzed by Western blotting to control for coating eYciency.…”

Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation and migration in human endothelial cells

“…To support this idea, microfibrils and RGD-containing fibrillin-1 fragments are already known to enhance adhesion, spreading, and migration of several cell types (5,6,14,47,53,54,61,70). Further support to this hypothesis was provided by 1) evidence that mice mutated for other microfibrillar components, e.g., fibulin-5 or emilin-1, have severe anomalies of vascular development and structure (51,73,74), and 2) the facts that mutations in the other main component of elastic fibers, elastin, cause Williams syndrome, and elastin fragments and tropoelastin have already been shown to influence Ca 2ϩ signaling, proliferation, and other functions in vascular and other types of cells (17,19,27,28,33,49,68).…”