Dataset Information

Extracellular matrix and integrin signalling: the shape of things to come.

ABSTRACT: The extracellular matrix (ECM) and integrins collaborate to regulate gene expression associated with cell growth, differentiation and survival. Biochemical and molecular analyses of integrin signalling pathways have uncovered several critical cytoplasmic proteins that link the ECM and integrins to intracellular pathways that may contribute to anchorage-dependent growth. A large body of evidence now indicates that the non-receptor protein kinases focal adhesion kinase (FAK) and specific members of the mitogen-activated protein kinases (MAPKs), including the extracellular-signal-regulated kinases (ERKs), mediate these ECM- and integrin-derived signalling events. However, little is known about how FAK and MAPKs contribute to biological processes other than cell proliferation or migration. In addition, remarkably little is known concerning the signalling events that occur in cells that adhere to complex multivalent extracellular matrices via multiple integrin receptors. Given the stringent requirement for attaining a proper morphology in ECM/integrin-directed cell behaviour, it is still not clear how cell shape and tissue architecture impact upon intracellular signalling programmes involving FAK and MAPKs. However, the recent discovery that members of the Rho family of small GTPases are able to regulate ECM/integrin pathways that modulate both cell shape and intracellular signalling provides new insights into how cell morphology and signal transduction become integrated, especially within three-dimensional differentiated tissues.

SUBMITTER: Boudreau NJ

PROVIDER: S-EPMC1220180 | biostudies-other | 1999 May

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Integrins provide the primary link between mesenchymal stem cells (MSCs) and their surrounding extracellular matrix (ECM), with different integrin pairs having specificity for different ECM molecules or peptide sequences contained within them. It is widely acknowledged that the type of ECM present can influence MSC differentiation; however, it is yet to be determined how specific integrin-ECM interactions may alter this or how they change during differentiation. We determined that human bone marrow-derived mesenchymal stem cells (hMSCs) express a broad range of integrins in their undifferentiated state and show a dramatic, but transient, increase in the level of ?5 integrin on day 7 of osteogenesis and an increase in ?6 integrin expression throughout adipogenesis. We used a nonfouling polystyrene-block-poly(ethylene oxide)-copolymer (PS-PEO) surface to present short peptides with defined integrin-binding capabilities (RGD, IKVAV, YIGSR, and RETTAWA) to hMSCs and investigate the effects of such specific integrin-ECM contacts on differentiation. hMSCs cultured on these peptides displayed different morphologies and had varying abilities to differentiate along the osteogenic and adipogenic lineages. The peptide sequences most conducive to differentiation (IKVAV for osteogenesis and RETTAWA and IKVAV for adipogenesis) were not necessarily those that were bound by those integrin subunits seen to increase during differentiation. Additionally, we also determined that presentation of RGD, which is bound by multiple integrins, was required to support long-term viability of hMSCs. Overall we confirm that integrin-ECM contacts change throughout hMSC differentiation and show that surfaces presenting defined peptide sequences can be used to target specific integrins and ultimately influence hMSC differentiation. This platform also provides information for the development of biomaterials capable of directing hMSC differentiation for use in tissue engineering therapies.

Project description:Historically, time preferences are modelled by assuming constant discounting, which implies a constant level of impatience. The prevailing empirical finding, however, is decreasing impatience (DI), meaning that levels of impatience decrease over time. Theoretically, such changes in impatience are crucial to understand behavior and self-control problems. Very few methods exist to measure DI without being restricted to or confounded by certain assumptions about the discounting function or utility curve. One such measure is the recently introduced DI-index, which has been applied to both monetary and health outcomes. The DI-index quantifies the deviation from constant impatience and is flexible enough to capture both increasing and decreasing impatience. In this study, we apply the DI-index to measure impatience for health outcomes in a reference-dependent framework. That is, we measure impatience for both health gains and health losses compared to a reference-point, in individual and societal settings, using a within-subjects design (n = 98). We allowed for both positive and negative discounting, since negative discounting has been observed for losses (i.e. preferring to incur losses earlier rather than later) in earlier work. To capture changes in time inconsistency when subjects show negative discounting (i.e. patience), we modify the DI-index to a decreasing (im)patience (DIP)-index, which can be applied without loss of generality. As in earlier work, we observe large heterogeneity in time consistency; i.e., a mix of decreasing, increasing and constant (im)patience. Across all DIP-indices elicited, increasing impatience was the modal preference for those satisfying impatience, and decreasing patience for those satisfying patience. No systematic differences were observed between health gains and losses or between societal and individual outcomes. This suggests that for health outcomes both patient and impatient individuals assign more importance to time differences delayed further in the future.

Dataset Information

Extracellular matrix and integrin signalling: the shape of things to come.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets