PubMed Health⌕ Search

Biomedical subjects

C Streuli

Publications and source records attributed to C Streuli.

9 recordsLinked to original sources
PubMed1999

Type IV collagen and laminin regulate glomerular mesangial cell susceptibility to apoptosis via beta(1) integrin-mediated survival signals.

Postinflammatory scarring is characterized by changes in extracellular matrix (ECM) composition and progressive loss of normal resident cells. In glomerular inflammation there is now evidence that unscheduled apoptosis (programmed cell death) of mesangial and other resident cells may mediate progression to irreversible glomerulosclerosis. In the current study we examined the hypothesis that ECM components may differ in their capacity to support mesangial cell survival by suppression of apoptosis. Using a well-established in vitro model of mesangial cell apoptosis, we found that collagen IV and laminin, components of normal mesangial ECM, protected rat mesangial cells from apoptosis induced by serum starvation and DNA damage, by a beta(1) integrin-mediated, but arg-gly-asp (RGD)-independent mechanism. In contrast, collagen I, fibronectin, and osteonectin/SPARC, which are overexpressed in diseased glomeruli, failed to promote rat mesangial cell survival. However, the survival-promoting effect of collagen IV and laminin was not associated with changes in cellular levels of apoptosis regulatory proteins of the Bcl-2 family. These experiments demonstrate that glomerular mesangial cell survival is dependent on interactions with ECM and provide insights into potential mechanisms by which resident cell loss may occur during acute inflammation and postinflammatory scarring of the kidney and other organs.

Animals↗
PubMed1999

Extracellular matrix remodelling and cellular differentiation.

The extracellular matrix is not merely a passive structure. In the past few years, it has emerged that the matrix is a dynamic action zone that functions to instruct cellular phenotype. Extracellular matrix proteins interact directly with cell surface receptors to initiate signal transduction pathways and to modulate those triggered by differentiation and growth factors. The extracellular matrix also controls the activity and presentation of a wide range of growth factors. Thus modulation of the extracellular matrix, by remodelling its structure and activity, has profound effects on its function and the consequent behaviour of cells residing on or within it.

Animals↗
PubMed1997

Division of labor of Schwann cell integrins during migration on peripheral nerve extracellular matrix ligands.

Myelination of the peripheral nervous system (PNS) requires the migration of Schwann cells during both development and regeneration. We have characterized the expression pattern of Schwann cell integrins and analyzed their role in migration on different ECM substrates known to be present within the PNS. We found that Schwann cells in cell culture express four beta1 integrins, alpha1 beta1, alpha2 beta1, alpha6 beta1, and another unidentified beta1 integrin, as well as two alpha v integrins, alpha v beta3 and alpha v beta8. Using the Varani migration assay, we found that laminin-1, laminin-2 (merosin), and fibronectin increased Schwann cell migration, while vitronectin and collagen did not increase migration compared to an uncoated plastic substrate. Schwann cell migration on laminin-1 and laminin-2 (merosin) was blocked by antibodies against beta1 integrins, but not affected by RGD peptides or antibodies against beta3 integrins. In contrast, migration on fibronectin was unaffected by antibodies against beta1 and beta3 integrins but was blocked by RGD peptides. This in vitro study shows that there is a division of labor of Schwann cell integrins in the regulation of migration on peripheral nerve ECM components; beta1 integrins mediate migration on laminin-1 and laminin-2 (merosin), while alpha v integrins mediate migration on fibronectin. Taken together, these results suggest that multiple interactions between Schwann cell integrins and ECM within the PNS will contribute to Schwann cell migration during myelination of the PNS.

Animals↗
PubMed1997

Epithelial apoptosis.

Apoptosis is an essential part of the normal cellular phenotype repertoire. In the absence of appropriate survival factors, apoptosis is activated through specific signalling cassettes. Epithelia form distinctive three-dimensional cohesive structures that depend on adhesive interactions in order for these tissues to carry out their specialised roles, such as secretion and reproduction. The cellular programme that triggers apoptosis in epithelial cells has not yet been shown to differ form that in other cell types, yet the unique characteristics of epithelia endow them with specific determinants for survival. In particular, cell-matrix and cell-cell interactions are required to prevent entry of epithelial cells into apoptosis, and soluble factors that have profound effects on epithelia, such as steroid hormones or hepatocyte growth factor, also influence their survival. The regenerative capacity of certain epithelia is controlled by intrinsic expression of survival genes within stem cell populations, and may regulate the susceptibility of different epithelial tissues to undergo carcinogenesis.

Animals↗
PubMed1997

Adhesion molecules involved in macrophage responses to Wallerian degeneration in the murine peripheral nervous system.

When a peripheral nerve is damaged the severed axon undergoes Wallerian degeneration. The distal nerve is infiltrated by large numbers of monocyte-derived macrophages which participate in the phagocytosis of degenerating myelin. In other tissues, adhesion molecules play a crucial role in leukocyte recruitment during inflammation. Blood-borne cells enter damaged tissue by interacting with adhesion molecules expressed on activated endothelium. Having crossed the endothelium, leukocytes must adhere and migrate within the tissue. We investigated the adhesion molecules involved in both stages of the macrophage response to transection of one sciatic nerve of BALB/c mice. By injecting monoclonal antibodies in vivo, before and after peripheral nerve injury, we showed that intercellular adhesion molecule-1 (ICAM-1) and integrins alpha4beta1 (VLA-4) and alphaMbeta2 (type 3 complement receptor) are unlikely to be involved in the transendothelial migration of monocytes responding to peripheral nerve degeneration. We also studied the adhesion of macrophages within the endoneurium, using an in vitro adhesion assay. Macrophages showed much greater levels of adhesion to cryostat sections of transected nerves than to control nerves. This increased adhesion was partially inhibited by antibodies to the beta1-integrin chain, and more strongly inhibited by the extracellular matrix molecules fibronectin and collagen. Adhesion was unaffected by laminin-1 and by antibodies to other adhesion molecules, including alpha4beta1- and alpha5beta1-integrins. Thus we conclude that monocyte entry into a degenerating peripheral nerve is independent of alphaLbeta2/alphaMbeta2-ICAM-1 or alpha4beta1/VCAM-1 interactions, and that adhesion within the endoneurium is mediated in part by a beta1-integrin other than alpha4beta1 or alpha5beta1.

Animals↗
PubMed1997

Expression of alpha vbeta3 and alpha vbeta8 integrins during oligodendrocyte precursor differentiation in the presence and absence of axons.

We have shown previously that switching of the alpha v-associated beta1 and beta5 integrin subunits during differentiation of myelin-forming oligodendrocytes may regulate important aspects of cell behaviour such as migration (Milner et al., 1996: J Neurosci 16:7240-7252). In this study we have examined the developmental regulation of other alpha v-associated beta subunits in oligodendroglial cell cultures and also the control of their expression by neurons, using xenocultures to distinguish glial and neuronal integrins. We have found that oligodendroglia express alpha vbeta8 in addition to the previously-described alpha vbeta1, alpha vbeta3, and alpha vbeta5. Beta8 and beta3 together comprise the 80kD band seen in alpha v immunoprecipitations that represents the most abundant alpha v-associated beta subunit and show reciprocal patterns of expression during development. Alpha vbeta8 is expressed at high levels on oligodendrocyte precursors and differentiated oligodendrocytes but diminishes during the intermediate stages of differentiation. Alpha vbeta3, in contrast, shows an opposite pattern of expression, with the highest levels seen at the intermediate stages of differentiation and little expression on either oligodendrocyte precursors and differentiated oligodendrocytes. The expression of alpha vbeta3 is not altered by coculture with neurons, unlike that of alpha vbeta8, in which the decrease seen at the intermediate stages of differentiation is less marked in the presence of neurones. Our results confirm that switching of alpha v-associated beta subunits is an important feature of oligodendrocyte differentiation and suggest that alpha vbeta8 and alpha vbeta3 have distinct functions during myelination.

Animals↗
PubMed1996

A role in migration for the alpha V beta 1 integrin expressed on oligodendrocyte precursors.

Myelination of the CNS requires the migration of oligodendrocyte precursors throughout the CNS from restricted regions within the ventricular and subventricular zones. In light of the significant effects of cell-extracellular matrix (ECM) interactions on cell migration in other developing systems, we have analyzed the role of integrins in oligodendrocyte precursor migration. We have shown previously that oligodendrocyte precursors in vitro express a limited repertoire of integrins, including alpha 6 beta 1, alpha v beta 3, and that differentiation is associated with downregulation of alpha v beta 1 and upregulation of alpha v beta 5. Using a migration assay based on the movement of cells away from an agarose drop containing a high-density cell suspension, we find that RGD peptides (that block alpha v but not alpha 6 integrins) and anti-beta 1 antibodies block migration on an astrocyte-derived ECM, whereas anti-beta 3 antibodies have little effect. These results suggest that alpha v beta 1 but not alpha 6 beta 1 plays a role in oligodendrocyte precursor migration, and this is confirmed by the use of blocking monoclonal antibodies that distinguish these two integrins. In keeping with the results of others, we find that differentiated oligodendrocytes lose migratory potential and that the timing of this loss correlates with downregulation of alpha v beta 1. Taken together with the work of others showing that ECM ligands for alpha v beta 1 are expressed within the CNS, we propose that this integrin plays a significant role in the migration of oligodendrocyte precursors in vivo and that its downregulation during differentiation could be an important factor regulating the migratory phenotype of these cells.

Animals↗
PubMed1995

Signalling in extracellular-matrix-mediated control of epithelial cell phenotype.

Interactions with an appropriate ECM are crucial for normal cell behaviour. The basement membrane contributes to both the tissue-specific lactational function and survival of mammary epithelial cells, possibly through a similar beta 1-integrin-dependent mechanism. Of current interest is whether the downstream intracellular signals diverge, with milk expression regulated through cell shape and the Jak-Stat pathway and survival mediated through controls on the Bcl-2/Bax and Ice checkpoints.

Animals↗