author_facet Nobe, Hiromi
Nobe, Koji
Paul, Richard J.
Nobe, Hiromi
Nobe, Koji
Paul, Richard J.
author Nobe, Hiromi
Nobe, Koji
Paul, Richard J.
spellingShingle Nobe, Hiromi
Nobe, Koji
Paul, Richard J.
American Journal of Physiology-Cell Physiology
Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
Cell Biology
Physiology
author_sort nobe, hiromi
spelling Nobe, Hiromi Nobe, Koji Paul, Richard J. 0363-6143 1522-1563 American Physiological Society Cell Biology Physiology http://dx.doi.org/10.1152/ajpcell.00067.2003 <jats:p>We investigated the mechanisms underlying regulation of contraction with measurements of isometric force and intracellular Ca<jats:sup>2+</jats:sup>concentration ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>) in NIH 3T3 fibroblast reconstituted into fibers with the use of a collagen matrix. Treatment with the major phospholipids, neurotransmitters, and growth factors had little effect on baseline isometric force. However, U-46619, a thromboxane A<jats:sub>2</jats:sub>(TxA<jats:sub>2</jats:sub>) analog, increased force and [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>; EC<jats:sub>50</jats:sub>values were 11.0 and 10.0 nM, respectively. The time courses were similar to those induced by calf serum (CS), and the maximal force was 65% of a CS-mediated contraction. The selective TxA<jats:sub>2</jats:sub>receptor antagonist SQ-29548 abolished the U-46619-induced responses. CS-induced contractions are dependent on an intracellular Ca<jats:sup>2+</jats:sup>store function; however, the U-46619 response depended not only on intracellular Ca<jats:sup>2+</jats:sup>stores, but also on Ca<jats:sup>2+</jats:sup>influx from the extracellular medium. Inhibition of Rho kinase suppressed U-46619- and CS-induced responses; in contrast, inhibition of C kinase (PKC) reduced only the U-46619 response. Moreover, addition of U-46619 to a CS contracture enhanced force and [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>responses. These results indicate that U-46619-induced responses involve PKC and Rho kinase pathways, in contrast to activation by CS. Thus TxA<jats:sub>2</jats:sub>may have a role in not only the initial step of wound repair as an activator of blood coagulation, but also in fibroblast contractility in later stages.</jats:p> Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A<sub>2</sub> American Journal of Physiology-Cell Physiology
doi_str_mv 10.1152/ajpcell.00067.2003
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series American Journal of Physiology-Cell Physiology
source_id 49
title Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_unstemmed Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_full Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_fullStr Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_full_unstemmed Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_short Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_sort fibroblast fiber contraction: role of c and rho kinase in activation by thromboxane a<sub>2</sub>
topic Cell Biology
Physiology
url http://dx.doi.org/10.1152/ajpcell.00067.2003
publishDate 2003
physical C1411-C1419
description <jats:p>We investigated the mechanisms underlying regulation of contraction with measurements of isometric force and intracellular Ca<jats:sup>2+</jats:sup>concentration ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>) in NIH 3T3 fibroblast reconstituted into fibers with the use of a collagen matrix. Treatment with the major phospholipids, neurotransmitters, and growth factors had little effect on baseline isometric force. However, U-46619, a thromboxane A<jats:sub>2</jats:sub>(TxA<jats:sub>2</jats:sub>) analog, increased force and [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>; EC<jats:sub>50</jats:sub>values were 11.0 and 10.0 nM, respectively. The time courses were similar to those induced by calf serum (CS), and the maximal force was 65% of a CS-mediated contraction. The selective TxA<jats:sub>2</jats:sub>receptor antagonist SQ-29548 abolished the U-46619-induced responses. CS-induced contractions are dependent on an intracellular Ca<jats:sup>2+</jats:sup>store function; however, the U-46619 response depended not only on intracellular Ca<jats:sup>2+</jats:sup>stores, but also on Ca<jats:sup>2+</jats:sup>influx from the extracellular medium. Inhibition of Rho kinase suppressed U-46619- and CS-induced responses; in contrast, inhibition of C kinase (PKC) reduced only the U-46619 response. Moreover, addition of U-46619 to a CS contracture enhanced force and [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>responses. These results indicate that U-46619-induced responses involve PKC and Rho kinase pathways, in contrast to activation by CS. Thus TxA<jats:sub>2</jats:sub>may have a role in not only the initial step of wound repair as an activator of blood coagulation, but also in fibroblast contractility in later stages.</jats:p>
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author Nobe, Hiromi, Nobe, Koji, Paul, Richard J.
author_facet Nobe, Hiromi, Nobe, Koji, Paul, Richard J., Nobe, Hiromi, Nobe, Koji, Paul, Richard J.
author_sort nobe, hiromi
container_issue 6
container_start_page 0
container_title American Journal of Physiology-Cell Physiology
container_volume 285
description <jats:p>We investigated the mechanisms underlying regulation of contraction with measurements of isometric force and intracellular Ca<jats:sup>2+</jats:sup>concentration ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>) in NIH 3T3 fibroblast reconstituted into fibers with the use of a collagen matrix. Treatment with the major phospholipids, neurotransmitters, and growth factors had little effect on baseline isometric force. However, U-46619, a thromboxane A<jats:sub>2</jats:sub>(TxA<jats:sub>2</jats:sub>) analog, increased force and [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>; EC<jats:sub>50</jats:sub>values were 11.0 and 10.0 nM, respectively. The time courses were similar to those induced by calf serum (CS), and the maximal force was 65% of a CS-mediated contraction. The selective TxA<jats:sub>2</jats:sub>receptor antagonist SQ-29548 abolished the U-46619-induced responses. CS-induced contractions are dependent on an intracellular Ca<jats:sup>2+</jats:sup>store function; however, the U-46619 response depended not only on intracellular Ca<jats:sup>2+</jats:sup>stores, but also on Ca<jats:sup>2+</jats:sup>influx from the extracellular medium. Inhibition of Rho kinase suppressed U-46619- and CS-induced responses; in contrast, inhibition of C kinase (PKC) reduced only the U-46619 response. Moreover, addition of U-46619 to a CS contracture enhanced force and [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>responses. These results indicate that U-46619-induced responses involve PKC and Rho kinase pathways, in contrast to activation by CS. Thus TxA<jats:sub>2</jats:sub>may have a role in not only the initial step of wound repair as an activator of blood coagulation, but also in fibroblast contractility in later stages.</jats:p>
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spelling Nobe, Hiromi Nobe, Koji Paul, Richard J. 0363-6143 1522-1563 American Physiological Society Cell Biology Physiology http://dx.doi.org/10.1152/ajpcell.00067.2003 <jats:p>We investigated the mechanisms underlying regulation of contraction with measurements of isometric force and intracellular Ca<jats:sup>2+</jats:sup>concentration ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>) in NIH 3T3 fibroblast reconstituted into fibers with the use of a collagen matrix. Treatment with the major phospholipids, neurotransmitters, and growth factors had little effect on baseline isometric force. However, U-46619, a thromboxane A<jats:sub>2</jats:sub>(TxA<jats:sub>2</jats:sub>) analog, increased force and [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>; EC<jats:sub>50</jats:sub>values were 11.0 and 10.0 nM, respectively. The time courses were similar to those induced by calf serum (CS), and the maximal force was 65% of a CS-mediated contraction. The selective TxA<jats:sub>2</jats:sub>receptor antagonist SQ-29548 abolished the U-46619-induced responses. CS-induced contractions are dependent on an intracellular Ca<jats:sup>2+</jats:sup>store function; however, the U-46619 response depended not only on intracellular Ca<jats:sup>2+</jats:sup>stores, but also on Ca<jats:sup>2+</jats:sup>influx from the extracellular medium. Inhibition of Rho kinase suppressed U-46619- and CS-induced responses; in contrast, inhibition of C kinase (PKC) reduced only the U-46619 response. Moreover, addition of U-46619 to a CS contracture enhanced force and [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>responses. These results indicate that U-46619-induced responses involve PKC and Rho kinase pathways, in contrast to activation by CS. Thus TxA<jats:sub>2</jats:sub>may have a role in not only the initial step of wound repair as an activator of blood coagulation, but also in fibroblast contractility in later stages.</jats:p> Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A<sub>2</sub> American Journal of Physiology-Cell Physiology
spellingShingle Nobe, Hiromi, Nobe, Koji, Paul, Richard J., American Journal of Physiology-Cell Physiology, Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2, Cell Biology, Physiology
title Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_full Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_fullStr Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_full_unstemmed Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_short Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
title_sort fibroblast fiber contraction: role of c and rho kinase in activation by thromboxane a<sub>2</sub>
title_unstemmed Fibroblast fiber contraction: role of C and Rho kinase in activation by thromboxane A2
topic Cell Biology, Physiology
url http://dx.doi.org/10.1152/ajpcell.00067.2003