Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells

Chen, Jianxin; Fabry, Ben; Schiffrin, Ernesto L.; Wang, Ning

doi:10.1152/ajpcell.2001.280.6.c1475

Cited by 178 publications

(95 citation statements)

References 52 publications

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“…To transmit the same force, a relatively stiff CSK would require less stretch than a more compliant CSK. Experiments by Chen et al (2001) tentatively support this idea. These investigators found that expression of endothelin-1 increases when integrin receptors in endothelial cells are twisted by attached microbeads, but this response is abolished when drugs are used to block cytoskeletal contraction.…”

Section: Primary Ingredients Of the Hyper-restoration Hypothesismentioning

confidence: 79%

Theoretical study of Beloussov’s hyper-restoration hypothesis for mechanical regulation of morphogenesis

Taber

2007

Biomech Model Mechanobiol

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Computational models were used to explore the idea that morphogenesis is regulated, in part, by feedback from mechanical stress according to Beloussov's Hyper-restoration (HR) Hypothesis. According to this hypothesis, active tissue responses to stress perturbations restore, but overshoot, the original (target) stress. To capture this behavior, the rate of growth or contraction is assumed to depend on the difference between the current and target stresses. Stress overshoot is obtained by letting the target stress change at a rate proportional to the same stress difference. The feasibility of the HR Hypothesis is illustrated by models for stretching of epithelia, cylindrical bending of plates, invagination of cylindrical and spherical shells, and early amphibian development. In each case, an initial perturbation leads to an active mechanical response that changes the form of the tissue. The results show that some morphogenetic processes can be entirely self-driven by HR responses once they are initiated (possibly by genetic activity). Other processes, however, may require secondary mechanisms or perturbations to proceed to completion.

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Section: Primary Ingredients Of the Hyper-restoration Hypothesismentioning

confidence: 79%

Theoretical study of Beloussov’s hyper-restoration hypothesis for mechanical regulation of morphogenesis

Taber

2007

Biomech Model Mechanobiol

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“…Twisting integrin receptors generates sufficient stress to activate mechanically sensitive genes (13). Models have been created to examine the amplitude and phase of bead rotation and displacement to estimate both solid and viscous characteristics (8,25).…”

Section: Techniques For Mechanically Probing Cellsmentioning

confidence: 99%

Cell mechanics and mechanotransduction: pathways, probes, and physiology

Huang

Kamm²,

Lee³

2004

American Journal of Physiology-Cell Physiology

487

367

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not only a complex biochemical environment but also a diverse biomechanical environment. How cells respond to variations in mechanical forces is critical in homeostasis and many diseases. The mechanisms by which mechanical forces lead to eventual biochemical and molecular responses remain undefined, and unraveling this mystery will undoubtedly provide new insight into strengthening bone, growing cartilage, improving cardiac contractility, and constructing tissues for artificial organs. In this article we review the physical bases underlying the mechanotransduction process, techniques used to apply controlled mechanical stresses on living cells and tissues to probe mechanotransduction, and some of the important lessons that we are learning from mechanical stimulation of cells with precisely controlled forces.cytoskeleton; micromanipulation; cell signaling ALL LIVING ORGANISMS face mechanical forces, from the fluid forces around a bacterium to the high forces in a human knee during stair climbing. The process of converting physical forces into biochemical signals and integrating these signals into the cellular responses is referred to as mechanotransduction. Although this review cannot cover all that has been discovered about mechanotransduction, we discuss the molecule-and cell-level structures that may participate in mechanotransduction, provide an overview of prominent techniques currently used for exerting mechanical stresses on cells, and conclude with an overview of the tissue-level response to mechanical signaling. FORCE TRANSDUCTION PATHWAYS AND SIGNALINGForce transmission pathways at the cellular and subcellular scales. Understanding the molecular basis for mechanotransduction requires knowledge of the magnitude and distribution of forces throughout the cell at the molecular scale. At present, we have sufficient information to measure molecular scale forces in only a very few cases. We can, however, analyze the mechanisms by which force is transmitted throughout the cell and use that as a basis for speculation about the molecular mechanisms of mechanotransduction. A variety of different methods have been used to mechanically stimulate a cell, and the cellular response is multifaceted and diverse. Similarly, there are likely to be a variety of sensing mechanisms and locations within the cell where forces can be transduced from a mechanical to a biochemical signal. Despite this apparent complexity, it is probable that cells stimulated in different ways are activated by similar mechanisms at the molecular level. To identify these commonalities, it is useful to consider how externally applied forces are transmitted into and throughout the cell, as well as the magnitudes and distribution of force corresponding to these different methods of stimulation.Both continuum and microstructural approaches have been used to determine force distributions. In the case of a continuum model, the details of the microstructure are ignored, and the forces transmitted via the individual microstructural elements are described in...

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“…It is worth noting that the integrin binding partners talin and paxillin that regulate cell adhesion, migration, and integrin conformation (57)(58)(59)(60)(61)(62)(63) could provide a means of mechanotransduction. That signaling has been documented with a magnetic drag force (64) to extend integrin molecules, generating an intracellular calcium response, gene transcription (65) and tyrosine phosphorylation (66 -68).…”

Section: Vla-4 Affinity Modulation By Shearmentioning

confidence: 99%

Real-time Analysis of Very Late Antigen-4 Affinity Modulation by Shear

Zwartz¹,

Chigaev²,

Dwyer

et al. 2004

Journal of Biological Chemistry

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Shear promotes endothelial recruitment of leukocytes, cell activation, and transmigration. Mechanical stress on cells caused by shear can induce a rapid integrin conformational change and activation, followed by an increase in binding to the extracellular matrix. The molecular mechanism of increased avidity is unknown. We have shown previously that the affinity of the ␣ 4 ␤ 1 integrin, very late antigen-4 (VLA-4), measured with an LDV-containing small molecule, varies with cellular avidity, measured from cell disaggregation rates. In this study, we measured in real time affinity changes of VLA-4 in response to shear. The resulting affinity was comparable with the state mediated by receptor signaling and corresponded in time with intracellular Ca 2؉ responses. Ca Leukocytes are recruited to endothelial cells in a multistep process using selectin and integrin adhesion molecules (1, 2). These molecules allow a cell to tether, roll, adhere, and transmigrate along and across an endothelial layer. Selectin and some integrin molecules and their associated ligands mediate tethering and rolling interactions. Firm adhesion is mediated by vascular ligands of the immunoglobulin superfamily such as vascular cell adhesion molecule 1 (VCAM-1) 1 and their associated integrins (1, 2). The adhesive strength or avidity (3) of cells expressing integrins can be rapidly modulated by chemokines and chemoattractants, which also regulate leukocyte recruitment and migration across vascular endothelium. The rapid changes in avidity have been attributed to changes in the number of interacting molecules or valency due to molecular redistribution or clustering and to changes in the affinity of the individual receptor-ligand bonds (3-10).Physiological shear can also regulate leukocyte traffic by stimulating mechanosensors on neutrophils, monocytes, lymphocytes, erythrocytes, and platelets (see Ref. 11 and references therein). Shear arises from bifurcating blood vessels or rapid changes in blood vessel diameters. Shear acting on leukocytes, bound to endothelial cells, produces mechanical stress on the cells or their receptors, regulating cell growth and proliferation, protein synthesis, gene expression, and blood cell recruitment (12, 13). Integrins (such as ␣ v ␤ 3 , ␣ 5 ␤ 1 , ␣ 4 ␤ 1 , and ␣ 2 ␤ 1 ) on endothelial cells can act as mechanosensors to changes in blood flow (13,14) and trigger an intracellular signaling pathway involving focal adhesion kinase and mitogen-activated protein kinase cascades. How shear specifically induces blood cell adhesiveness or recruitment through mechanosensors is unknown. Indirect evidence shows that increased integrin binding to the extracellular matrix occurs when shear acts on cells or their mechanosensors to induce intracellular signaling. For example, intracellular signaling leads to conformational changes and activation of ␣ v ␤ 3 on endothelial cells and ␣ 4 ␤ 1 and ␣ 5 ␤ 1 integrins on monocytic cells (15, 16). Shear acting on endothelial cells affects the GTPase Rho signaling pathway and in monocyti...

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Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells

Cited by 178 publications

References 52 publications

Theoretical study of Beloussov’s hyper-restoration hypothesis for mechanical regulation of morphogenesis

Theoretical study of Beloussov’s hyper-restoration hypothesis for mechanical regulation of morphogenesis

Cell mechanics and mechanotransduction: pathways, probes, and physiology

Real-time Analysis of Very Late Antigen-4 Affinity Modulation by Shear

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