Phosphorylation Of Vasodilator-Stimulated Phosphoprotein (VASP) Regulates Contractility Of Airway Smooth Muscle Tissues By Regulating Actin Dynamics

2010 ◽  
Author(s):  
Yidi Wu ◽  
Bhargavi Vemuri ◽  
Susan J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Actin Dynamics ◽  
Muscle Tissues

scholarly journals Mechanical stimuli and IL-13 interact at integrin adhesion complexes to regulate expression of smooth muscle myosin heavy chain in airway smooth muscle tissue

2011 ◽  
Vol 301 (3) ◽  
pp. L275-L284 ◽  
Author(s):  
Leena P. Desai ◽  
Yidi Wu ◽  
Robert S. Tepper ◽  
Susan J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Airway Smooth Muscle ◽  
Heavy Chain ◽  
High Load ◽  
Phenotypic Marker ◽  
Akt Activation ◽  
Muscle Tissues ◽  
Low Load ◽  
Muscle Myosin

Airway smooth muscle phenotype may be modulated in response to external stimuli under physiological and pathophysiological conditions. The effect of mechanical forces on airway smooth muscle phenotype were evaluated in vitro by suspending weights of 0.5 or 1 g from the ends of canine tracheal smooth muscle tissues, incubating the weighted tissues for 6 h, and then measuring the expression of the phenotypic marker protein, smooth muscle myosin heavy chain (SmMHC). Incubation of the tissues at a high load significantly increased expression of SmMHC compared with incubation at low load. Incubation of the tissues at a high load also decreased activation of PKB/Akt, as indicated by its phosphorylation at Ser 473. Inhibition of Akt or phosphatidylinositol-3,4,5 triphosphate-kinase increased SmMHC expression in tissues at low load but did not affect SmMHC expression at high load. IL-13 induced a significant increase in Akt activation and suppressed the expression of SmMHC protein at both low and high loads. The role of integrin signaling in mechanotransduction was evaluated by expressing a PINCH (LIM1–2) fragment in the muscle tissues that prevents the membrane localization of the integrin-binding IPP complex (ILK/PINCH/α-parvin), and also by expressing an inactive integrin-linked kinase mutant (ILK S343A) that inhibits endogenous ILK activity. Both mutants inhibited Akt activation and increased expression of SmMHC protein at low load but had no effect at high load. These results suggest that mechanical stress and IL-13 both act through an integrin-mediated signaling pathway to oppositely regulate the expression of phenotypic marker proteins in intact airway smooth muscle tissues. The stimulatory effects of mechanical stress on contractile protein expression oppose the suppression of contractile protein expression mediated by IL-13; thus the imposition of mechanical strain may inhibit changes in airway smooth muscle phenotype induced by inflammatory mediators.

Effects of Bronchodilators Combined With Oscillations on the Contracted Airway Smooth Muscle

2010 ◽  
Author(s):  
M. Mathur ◽  
A. M. Al-Jumaily ◽  
G. Ijpma ◽  
R. Alany
Keyword(s):  
Smooth Muscle ◽  
Side Effects ◽  
Airway Smooth Muscle ◽  
Muscle Relaxants ◽  
Combined Effects ◽  
In Vitro Experiments ◽  
Current Asthma ◽  
Cardiovascular Side Effects ◽  
Muscle Tissues

Current asthma treatments using anti-inflammatory agents and airway smooth muscle (ASM) relaxants are expensive, variable in effectiveness and are associated with several cardiovascular side effects. Previous in vitro experiments conducted on ASM tissues suggest that oscillations applied to contracted muscle result in a reduction in the contractile ability of the tissue. This study focuses on investigating the combined effects of muscle relaxants (bronchodilators) and length oscillations on the dynamics of contracted ASM. Isolated porcine tracheal smooth muscle tissues are contracted using Acetylcholine. Isoproterenol (Iso), a β-agonist, is used as a bronchodilator to relax the contracted ASM. Our results suggest that the combined effect of Iso and breathing oscillations is noted to be greater than the added effects of Iso and breathing alone. It can be proposed that breathing oscillations aid the relaxation of ASM by Isoproterenol.

The Proprotein Convertase Furin inhibits IL-13 Induced Inflammation in Airway Smooth Muscle by Regulating Integrin Associated Signaling Complexes

2021 ◽  
Author(s):  
Yidi Wu ◽  
Youliang Huang ◽  
Wenwu Zhang ◽  
Susan J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Proprotein Convertase ◽  
Akt Activation ◽  
Inflammatory Conditions ◽  
Muscle Tissues ◽  
Muscle Myosin

Furin is a proprotein convertase that regulates the activation and inactivation of multiple proteins including matrix metalloproteinases, integrins and cytokines. It is a serine endoprotease that localizes to the plasma membrane and can be secreted into the extracellular space. The role of furin in regulating inflammation in isolated canine airway smooth muscle tissues was investigated. The treatment of airway tissues with recombinant furin (rFurin) inhibited the activation of Akt and eotaxin secretion induced by IL-13, and it prevented the IL-13 induced suppression of smooth muscle myosin heavy chain expression. rFurin promoted a differentiated phenotype by activating β1 integrin proteins and stimulating the activation of the adhesome proteins vinculin and paxillin by talin. Activated paxillin induced the binding of Akt to β-parvin IPP (ILK, PINCH, parvin) complexes, which inhibits Akt activation. Treatment of tissues with a furin inhibitor or the depletion of endogenous furin using shRNA resulted in Akt activation and inflammatory responses similar to those induced by IL-13. Furin inactivation or IL-13 caused talin cleavage and integrin inactivation, resulting in the inactivation of vinculin and paxillin. Paxillin inactivation resulted in the coupling of Akt to α-parvin IPP complexes, which catalyze Akt activation and an inflammatory response. The results demonstrate that furin inhibits inflammation in airway smooth muscle induced by IL-13, and that the anti-inflammatory effects of furin are mediated by activating integrin proteins and integrin-associated signaling complexes that regulate Akt-mediated pathways to the nucleus. Furin may have therapeutic potential for the treatment of inflammatory conditions of the lungs and airways.

Studies of the mechanism of passive anaphylaxis in human airway smooth muscle

1983 ◽  
Vol 61 (7) ◽  
pp. 705-713 ◽  
Author(s):  
C. Davis ◽  
T. R. Jones ◽  
E. E. Daniel
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Immunoglobulin E ◽  
Specific Antigen ◽  
Maximal Response ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Muscle Tissues ◽  
Acid Metabolites

This investigation was carried out to study allergic contraction of passively sensitized human airway smooth muscle in response to specific antigen challenge. We attempted to determine the role played by histamine, slow reaction substances (SRSs), and cyclooxygenase products in the mediation of this response in tracheal smooth muscle. Tissues were passively sensitized with serum from ragweed-sensitive patients (15 h, 4 °C). Subsequent challenge with ragweed antigen produced a slowly developing contraction. The peak contraction to a dose producing a maximal response was 37 ± 6% of the carbachol maximum. Mepyramine (5 × 10−6 M) did not alter the contraction. Methylprednisolone (2 × 10−5 M) attenuated the response to antigen but had no significant effect on the contractile response to arachidonic acid. Indomethacin (5.6–28 × 10−6 M) enhanced the peak antigen-induced contractions by 25 ± 11% whereas 5, 8, 11, 14-eicosatetraynoic acid (6.4 × 10−5 M) selectively attenuated the antigen-induced contraction by 86 ± 12%. Nordihydroguarietic acid (6–12 × 10−6 M) attenuated both the antigen plus arachidonate induced responses. FPL-55712 (1–2 × 10−6 M) antagonized the contractions to antigen. Compound 48/80 and goat antihuman immunoglobulin E produced similar slowly developing contractions in sensitized and in some nonsensitized tissues. These responses, except for an early component of the response to 48/80, were independent of histamine and were reversed by FPL-55712. These findings suggest that arachidonic acid metabolites mediate (slow reacting substances) and modulate (prostaglandins) allergic contraction of human airway smooth muscle while any histamine released contributes little or nothing to the contraction in the larger airways.

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