Caveolin-1 and force regulation in porcine airway smooth muscle

Venkatachalem Sathish, Binxia Yang, Lucas W. Meuchel, Sarah K. VanOosten, Alexander J. Ryu, Michael A. Thompson, Y.s. Prakash, Christina M Pabelick

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Caveolae are specialized membrane microdomains expressing the scaffolding protein caveolin-1. We recently demonstrated the presence of caveolae in human airway smooth muscle (ASM) and the contribution of caveolin-1 to intracellular calcium ([Ca2+]i) regulation. In the present study, we tested the hypothesis that caveolin-1 regulates ASM contractility. We examined the role of caveolins in force regulation of porcine ASM under control conditions as well as TNF-α-induced airway inflammation. In porcine ASM strips, exposure to 10 mM methyl-β-cyclodextrin (CD) or 5 μM of the caveolin-1 specific scaffolding domain inhibitor peptide (CSD) resulted in time-dependent decrease in force responses to 1 μM ACh. Overnight exposure to the cytokine TNF-α (50 ng/ml) accelerated and increased caveolin-1 expression and enhanced force responses to ACh. Suppression of caveolin-1 with small interfering RNA mimicked the effects of CD or CSD. Regarding mechanisms by which caveolae contribute to contractile changes, inhibition of MAP kinase with 10 μM PD98059 did not alter control or TNF-α-induced increases in force responses to ACh. However, inhibiting RhoA with 100 μM fasudil or 10 μM Y27632 resulted in significant decreases in force responses, with lesser effects in TNF-α exposed samples. Furthermore, Ca2+ sensitivity for force generation was substantially reduced by fasudil or Y27632, an effect even more enhanced in the absence of caveolin-1 signaling. Overall, these results indicate that caveolin-1 is a critical player in enhanced ASM contractility with airway inflammation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume300
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Caveolin 1
Smooth Muscle
Swine
Caveolae
Caveolin 3
Cyclodextrins
Membrane Microdomains
Caveolins
Inflammation
Small Interfering RNA
Phosphotransferases
Cytokines
Calcium

Keywords

  • Caveolae
  • Cytokine
  • Inflammation
  • Lung
  • MAP kinase
  • RhoA
  • Small interfering RNA

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Caveolin-1 and force regulation in porcine airway smooth muscle. / Sathish, Venkatachalem; Yang, Binxia; Meuchel, Lucas W.; VanOosten, Sarah K.; Ryu, Alexander J.; Thompson, Michael A.; Prakash, Y.s.; Pabelick, Christina M.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 300, No. 6, 06.2011.

Research output: Contribution to journalArticle

Sathish, Venkatachalem ; Yang, Binxia ; Meuchel, Lucas W. ; VanOosten, Sarah K. ; Ryu, Alexander J. ; Thompson, Michael A. ; Prakash, Y.s. ; Pabelick, Christina M. / Caveolin-1 and force regulation in porcine airway smooth muscle. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2011 ; Vol. 300, No. 6.
@article{9f55ab4389264e7f858364cea2d66a93,
title = "Caveolin-1 and force regulation in porcine airway smooth muscle",
abstract = "Caveolae are specialized membrane microdomains expressing the scaffolding protein caveolin-1. We recently demonstrated the presence of caveolae in human airway smooth muscle (ASM) and the contribution of caveolin-1 to intracellular calcium ([Ca2+]i) regulation. In the present study, we tested the hypothesis that caveolin-1 regulates ASM contractility. We examined the role of caveolins in force regulation of porcine ASM under control conditions as well as TNF-α-induced airway inflammation. In porcine ASM strips, exposure to 10 mM methyl-β-cyclodextrin (CD) or 5 μM of the caveolin-1 specific scaffolding domain inhibitor peptide (CSD) resulted in time-dependent decrease in force responses to 1 μM ACh. Overnight exposure to the cytokine TNF-α (50 ng/ml) accelerated and increased caveolin-1 expression and enhanced force responses to ACh. Suppression of caveolin-1 with small interfering RNA mimicked the effects of CD or CSD. Regarding mechanisms by which caveolae contribute to contractile changes, inhibition of MAP kinase with 10 μM PD98059 did not alter control or TNF-α-induced increases in force responses to ACh. However, inhibiting RhoA with 100 μM fasudil or 10 μM Y27632 resulted in significant decreases in force responses, with lesser effects in TNF-α exposed samples. Furthermore, Ca2+ sensitivity for force generation was substantially reduced by fasudil or Y27632, an effect even more enhanced in the absence of caveolin-1 signaling. Overall, these results indicate that caveolin-1 is a critical player in enhanced ASM contractility with airway inflammation.",
keywords = "Caveolae, Cytokine, Inflammation, Lung, MAP kinase, RhoA, Small interfering RNA",
author = "Venkatachalem Sathish and Binxia Yang and Meuchel, {Lucas W.} and VanOosten, {Sarah K.} and Ryu, {Alexander J.} and Thompson, {Michael A.} and Y.s. Prakash and Pabelick, {Christina M}",
year = "2011",
month = "6",
doi = "10.1152/ajplung.00322.2010",
language = "English (US)",
volume = "300",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "6",

}

TY - JOUR

T1 - Caveolin-1 and force regulation in porcine airway smooth muscle

AU - Sathish, Venkatachalem

AU - Yang, Binxia

AU - Meuchel, Lucas W.

AU - VanOosten, Sarah K.

AU - Ryu, Alexander J.

AU - Thompson, Michael A.

AU - Prakash, Y.s.

AU - Pabelick, Christina M

PY - 2011/6

Y1 - 2011/6

N2 - Caveolae are specialized membrane microdomains expressing the scaffolding protein caveolin-1. We recently demonstrated the presence of caveolae in human airway smooth muscle (ASM) and the contribution of caveolin-1 to intracellular calcium ([Ca2+]i) regulation. In the present study, we tested the hypothesis that caveolin-1 regulates ASM contractility. We examined the role of caveolins in force regulation of porcine ASM under control conditions as well as TNF-α-induced airway inflammation. In porcine ASM strips, exposure to 10 mM methyl-β-cyclodextrin (CD) or 5 μM of the caveolin-1 specific scaffolding domain inhibitor peptide (CSD) resulted in time-dependent decrease in force responses to 1 μM ACh. Overnight exposure to the cytokine TNF-α (50 ng/ml) accelerated and increased caveolin-1 expression and enhanced force responses to ACh. Suppression of caveolin-1 with small interfering RNA mimicked the effects of CD or CSD. Regarding mechanisms by which caveolae contribute to contractile changes, inhibition of MAP kinase with 10 μM PD98059 did not alter control or TNF-α-induced increases in force responses to ACh. However, inhibiting RhoA with 100 μM fasudil or 10 μM Y27632 resulted in significant decreases in force responses, with lesser effects in TNF-α exposed samples. Furthermore, Ca2+ sensitivity for force generation was substantially reduced by fasudil or Y27632, an effect even more enhanced in the absence of caveolin-1 signaling. Overall, these results indicate that caveolin-1 is a critical player in enhanced ASM contractility with airway inflammation.

AB - Caveolae are specialized membrane microdomains expressing the scaffolding protein caveolin-1. We recently demonstrated the presence of caveolae in human airway smooth muscle (ASM) and the contribution of caveolin-1 to intracellular calcium ([Ca2+]i) regulation. In the present study, we tested the hypothesis that caveolin-1 regulates ASM contractility. We examined the role of caveolins in force regulation of porcine ASM under control conditions as well as TNF-α-induced airway inflammation. In porcine ASM strips, exposure to 10 mM methyl-β-cyclodextrin (CD) or 5 μM of the caveolin-1 specific scaffolding domain inhibitor peptide (CSD) resulted in time-dependent decrease in force responses to 1 μM ACh. Overnight exposure to the cytokine TNF-α (50 ng/ml) accelerated and increased caveolin-1 expression and enhanced force responses to ACh. Suppression of caveolin-1 with small interfering RNA mimicked the effects of CD or CSD. Regarding mechanisms by which caveolae contribute to contractile changes, inhibition of MAP kinase with 10 μM PD98059 did not alter control or TNF-α-induced increases in force responses to ACh. However, inhibiting RhoA with 100 μM fasudil or 10 μM Y27632 resulted in significant decreases in force responses, with lesser effects in TNF-α exposed samples. Furthermore, Ca2+ sensitivity for force generation was substantially reduced by fasudil or Y27632, an effect even more enhanced in the absence of caveolin-1 signaling. Overall, these results indicate that caveolin-1 is a critical player in enhanced ASM contractility with airway inflammation.

KW - Caveolae

KW - Cytokine

KW - Inflammation

KW - Lung

KW - MAP kinase

KW - RhoA

KW - Small interfering RNA

UR - http://www.scopus.com/inward/record.url?scp=79958207253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958207253&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00322.2010

DO - 10.1152/ajplung.00322.2010

M3 - Article

C2 - 21421751

AN - SCOPUS:79958207253

VL - 300

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 6

ER -