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Twisting integrin receptors increases endothelin-1 gene expression in endothelial cellsA magnetic twisting stimulator was developed based on the previously published technique of magnetic twisting cytometry. Using ligand-coated ferromagnetic microbeads, this device can apply mechanical stresses with varying amplitudes, duration, frequencies, and waveforms to specific cell surface receptors. Biochemical and biological responses of the cells to the mechanical stimulation can be assayed. Twisting integrin receptors with RGD (Arg-Gly-Asp)-containing peptide-coated beads increased endothelin-1 (ET-1) gene expression by >100%. In contrast, twisting scavenger receptors with acetylated low-density lipoprotein-coated beads or twisting HLA antigen with anti-HLA antibody-coated beads did not lead to alterations in ET-1 gene expression. In situ hybridization showed that the increase in ET-1 mRNA was localized in the cells that were stressed with the RGD-coated beads. Blocking stretch-activated ion channels with gadolinium, chelating Ca2+ with EGTA, or inhibiting tyrosine phosphorylation with genistein abolished twist-induced ET-1 mRNA elevation. Abolishing cytoskeletal tension with an inhibitor of the myosin ATPase, with an inhibitor of myosin light chain kinase, or with an actin microfilament disrupter blocked twisted-induced increases in ET-1 expression. Our results are consistent with the hypothesis that the molecular structural linkage of integrin-cytoskeleton is an important pathway for stress-induced ET-1 gene expression.
Document ID
20040112449
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Chen, J.
(Harvard School of Public Health 665 Huntington Avenue, Boston, MA 02115, United States)
Fabry, B.
Schiffrin, E. L.
Wang, N.
Ingber, D. E.
Date Acquired
August 21, 2013
Publication Date
June 1, 2001
Publication Information
Publication: American journal of physiology. Cell physiology
Volume: 280
Issue: 6
ISSN: 0363-6143
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL-65371
CONTRACT_GRANT: HL-33009
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Cell Biology

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