Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice

Chiba, Yoshihiko; Ueno, Ayako; Shinozaki, Koji; Takeyama, Hisao; Nakazawa, Shuji; Sakai, Hiroyasu; Misawa, Miwa

doi:10.1186/1465-9921-6-4

Cited by 89 publications

(140 citation statements)

References 39 publications

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“…In animal models of allergic bronchial asthma, an in vivo airway hyperresponsiveness accompanied by the increased IgE production and pulmonary eosinophilia has been demonstrated (Misawa and Chiba, 1993;Kato et al, 1999;Chiba et al, 2008). In these models of airway hyperresponsiveness, an increased contractility of isolated BSM to contractile agonists has also been found (Misawa and -518 to -510, -271 to -263, -191 to -183, and -78 to -70 bp) Chiba, 1993;Chiba and Misawa, 1995;Chiba et al, 2005;2008;2009a). The augmented BSM contraction induced by antigen exposure has reportedly been associated with an upregulation of RhoA (Chiba et al, 1999;2003;2005;2008;2009a;2009b;2009c), a small GTPase that is involved in the agonist-induced Ca 2+ sensitization of smooth muscle contraction (Somlyo and Somlyo 2003;Chiba and Misawa, 2004).…”

Section: Discussionmentioning

confidence: 94%

“…In these models of airway hyperresponsiveness, an increased contractility of isolated BSM to contractile agonists has also been found (Misawa and -518 to -510, -271 to -263, -191 to -183, and -78 to -70 bp) Chiba, 1993;Chiba and Misawa, 1995;Chiba et al, 2005;2008;2009a). The augmented BSM contraction induced by antigen exposure has reportedly been associated with an upregulation of RhoA (Chiba et al, 1999;2003;2005;2008;2009a;2009b;2009c), a small GTPase that is involved in the agonist-induced Ca 2+ sensitization of smooth muscle contraction (Somlyo and Somlyo 2003;Chiba and Misawa, 2004). The RhoA and its downstream Rho-kinases are now considered as a target of airway obstructive diseases such as asthma (Gosens et al, 2006;Kume, 2008;Schaafsma et al, 2008a;2008b).…”

Section: Discussionmentioning

confidence: 99%

“…There is increasing evidence that a monomeric GTP-binding protein, RhoA, and its downstream target, Rho-kinases, are involved in the Ca 2+ -independent contraction (termed Ca 2+ sensitization) of airway smooth muscles (Chiba et al, 1999;2005;Ito et al, 2001;Yoshii et al, 1999). When the RhoA/Rho-kinase system is activated by contractile agonists, the activity of myosin light chain (MLC) phosphatase is reduced and the level of phosphorylated MLC is in turn increased, resulting in an augmentation of contraction.…”

Section: Introductionmentioning

confidence: 99%

“…When the RhoA/Rho-kinase system is activated by contractile agonists, the activity of myosin light chain (MLC) phosphatase is reduced and the level of phosphorylated MLC is in turn increased, resulting in an augmentation of contraction. Recent studies demonstrated that the agonist-induced, RhoA/Rho-kinase-mediated Ca 2+ sensitization of bronchial smooth muscle (BSM) contraction is augmented in rats (Chiba et al, 1999) and mice (Chiba et al, 2005) with allergic bronchial asthma. An importance of the RhoA/Rho-kinase system has also been demonstrated in human BSM (Yoshii et al, 1999), and the signaling of RhoA and its downstream Rho-kinases are now considered as a therapeutic target for the treatment of airway hyperresponsiveness in asthma (Gosens et al, 2006;Kume, 2008;Schaafsma et al, 2008a;2008b).…”

Section: Introductionmentioning

confidence: 99%

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Induction of RhoA gene expression by interleukin-4 in cultured human bronchial smooth muscle cells

Chiba

Goto

Momata

et al. 2010

J. Smooth Muscle Res.

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RhoA, a small GTPase, is one of the key proteins of smooth muscle contraction. In allergic asthma, an upregulation of RhoA in bronchial smooth muscle has been suggested. However, the mechanism of its upregulation has not yet been clarified. In the present study, the effects of interleukin-4 (IL-4), one of the T-helper 2 cytokines, on RhoA mRNA expression and promoter activity of RhoA gene were examined in cultured human bronchial smooth muscle cells (hBSMCs). The quantitative real-time RT-PCR analyses revealed that incubation of hBSMCs with IL-4 (10, 30 and 100 ng/mL, for 24 hr) caused an increase in RhoA mRNA in a concentration-dependent manner. In luciferase reporter gene assay using hBSMCs that were transfected with luciferase constructs and were then stimulated with IL-4 (100 ng/mL), an importance of the most proximal STAT6 binding region (78-70 bp upstream of the transcription initiation site) was suggested. It is thus possible that IL-4 is capable of upregulating RhoA by promoting its transcription in hBSMCs. The proximal STAT6 binding region is required for the IL-4-induced increase in promoter activity of the human RhoA gene.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Induction of RhoA gene expression by interleukin-4 in cultured human bronchial smooth muscle cells

Chiba

Goto

Momata

et al. 2010

J. Smooth Muscle Res.

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“…RhoA is a key protein in smooth muscle contraction and its upregulation is associated with the augmented contraction of bronchial smooth muscle [122,123].…”

Section: Asthmamentioning

confidence: 99%

MicroRNAs and respiratory diseases

2012

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MicroRNAs (miRNAs) are a family of endogenous, small, noncoding RNA molecules that modulate physiological and pathological processes by post-transcriptional inhibition of gene expression. They were first recognised as regulators of development in worms and fruitflies. In recent years extensive research has explored their pivotal role in the pathogenesis of human diseases. Over 1,000 human miRNAs have been discovered to date; however, the biological function and protein targets for the majority remain to be uncovered. Within the respiratory system, miRNAs are important in normal pulmonary development and maintaining lung homeostasis. Recent studies have also begun to reveal that altered miRNA expression profiles may be associated with pathological processes within the lung and lead to the development of various pulmonary diseases, ranging from inflammatory diseases to lung cancers. Advancing our understanding of the role of miRNAs in the respiratory system will help provide new perspectives on disease mechanisms and reveal intriguing therapeutic targets and diagnostic markers for respiratory disorders.

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Folium Sennae and emodin reverse airway smooth muscle contraction

Qiu¹,

Ma²,

Liu³

et al. 2020

Cell Biology International

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The objective of this project was to find a bronchodilatory compound from herbs and clarify the mechanism. We found that the ethanol extract of Folium Sennae (EEFS) can relax airway smooth muscle (ASM). EEFS inhibited ASM contraction, induced by acetylcholine, in mouse tracheal rings and lung slices. High‐performance liquid chromatography assay showed that EEFS contained emodin. Emodin had a similar reversal action. Acetylcholine‐evoked contraction was also partially reduced by nifedipine (a selective inhibitor of L‐type voltage‐dependent Ca2+ channels, LVDCCs), YM‐58483 (a selective inhibitor of store‐operated Ca2+ entry, SOCE), as well as Y‐27632 (an inhibitor of Rho‐associated protein kinase). In addition, LVDCC‐ and SOCE‐mediated currents and cytosolic Ca2+ elevations were inhibited by emodin. Emodin reversed acetylcholine‐caused increases in phosphorylation of myosin phosphatase target subunit 1. Furthermore, emodin, in vivo, inhibited acetylcholine‐induced respiratory system resistance in mice. These results indicate that EEFS‐induced relaxation results from emodin inhibiting LVDCC, SOCE, and Ca2+ sensitization. These findings suggest that Folium Sennae and emodin may be new sources of bronchodilators.

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Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice

Cited by 89 publications

References 39 publications

Induction of RhoA gene expression by interleukin-4 in cultured human bronchial smooth muscle cells

Induction of RhoA gene expression by interleukin-4 in cultured human bronchial smooth muscle cells

MicroRNAs and respiratory diseases

Folium Sennae and emodin reverse airway smooth muscle contraction

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