Augmented PDBu-mediated contraction of bronchial smooth muscle of mice with antigen-induced airway hyperresponsiveness

Sakai, Hiroyasu; Kurihara, Yusuke; Hashimoto, Yuki; Chiba, Yoshihiko; Misawa, Miwa

doi:10.1540/jsmr.46.259

Cited by 2 publications

(2 citation statements)

References 28 publications

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“…Upon contractile agonist stimulation of hyperresponsive BSMs PKC/CPI-17 signaling activity increased by CPI-17 upregulation. Indeed, the phorbol 12,13-dibutyrate-mediated contraction was markedly augmented in BSMs of AHR animals (78). ACh-induced phosphorylation of CPI-17 at Thr38 was significantly increased in BSMs of AHR animals.…”

Section: Involvement Of Cpi-17 In Smooth Muscle Contractionmentioning

confidence: 99%

Mechanisms underlying the pathogenesis of hyper-contractility of bronchial smooth muscle in allergic asthma

Sakai

Suto

Kai

et al. 2017

J. Smooth Muscle Res.

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Airway hyperresponsiveness (AHR) and inflammation are key pathophysiological features of asthma. Enhanced contraction of bronchial smooth muscle (BSM) is one of the causes of the AHR. It is thus important for development of asthma therapy to understand the change in the contractile signaling of airway smooth muscle cells associated with the AHR. In addition to the Ca2+-mediated phosphorylation of myosin light chain (MLC), contractile agonists also enhance MLC phosphorylation level, Ca2+-independently, by inactivating MLC phosphatase (MLCP), called Ca2+ sensitization of contraction, in smooth muscle cells including airways. To date, involvements of RhoA/ROCKs and PKC/Ppp1r14a (also called as CPI-17) pathways in the Ca2+ sensitization have been identified. Our previous studies revealed that the agonist-induced Ca2+ sensitization of contraction is markedly augmented in BSMs of animal models of allergen-induced AHR. In BSMs of these animal models, the expression of RhoA and CPI-17 proteins were significantly increased, indicating that both the Ca2+ sensitizing pathways are augmented. Interestingly, incubation of BSM cells with asthma-associated cytokines, such as interleukin-13 (IL-13), IL-17, and tumor necrosis factor-α (TNF-α), caused up-regulations of RhoA and CPI-17 in BSM cells of naive animals and cultured human BSM cells. In addition to the transcription factors such as STAT6 and NF-κB activated by these inflammatory cytokines, an involvement of down-regulation of miR-133a, a microRNA that negatively regulates RhoA translation, has also been suggested in the IL-13- and IL-17-induced up-regulation of RhoA. Thus, the Ca2+ sensitizing pathways and the cytokine-mediated signaling including microRNAs in BSMs might be potential targets for treatment of allergic asthma, especially the AHR.

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Section: Involvement Of Cpi-17 In Smooth Muscle Contractionmentioning

confidence: 99%

Mechanisms underlying the pathogenesis of hyper-contractility of bronchial smooth muscle in allergic asthma

Sakai

Suto

Kai

et al. 2017

J. Smooth Muscle Res.

Self Cite

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“…Upon contractile agonist stimulation of hyperresponsive BSM PKC/CPI-17 signaling activity increased by CPI-17 upregulation. Indeed, the phorbol 12,13-dibutyrate-mediated contraction was markedly augmented in BSM of AHR animals(104). ACh-induced phosphorylation of CPI-17 at Thr38 was significantly increased in BSM of AHR animals(Fig.…”

mentioning

confidence: 78%

Implications of immune-inflammatory responses in smooth muscle dysfunction and disease

Usui-Kawanishi

Takahashi

Sakai

et al. 2019

J Smooth Muscle Res

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In the past few decades, solid evidence has been accumulated for the pivotal significance of immunoinflammatory processes in the initiation, progression, and exacerbation of many diseases and disorders. This groundbreaking view came from original works by Ross who first described that excessive inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall is essential for the pathogenesis of atherosclerosis (Ross, Nature 1993; 362(6423): 801-9). It is now widely recognized that both innate and adaptive immune reactions are avidly involved in the inflammation-related remodeling of many tissues and organs. When this state persists, irreversible fibrogenic changes would occur often culminating in fatal insufficiencies of many vital parenchymal organs such as liver, lung, heart, kidney and intestines. Thus, inflammatory diseases are becoming the common life-threatening risk for and urgent concern about the public health in developed countries (Wynn et al., Nature Medicine 2012; 18(7): 1028-40). Considering this timeliness, we organized a special symposium entitled "Implications of immune/inflammatory responses in smooth muscle dysfunction and disease" in the 58th annual meeting of the Japan Society of Smooth Muscle Research. This symposium report will provide detailed synopses of topics presented in this symposium; (1) the role of

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Augmented PDBu-mediated contraction of bronchial smooth muscle of mice with antigen-induced airway hyperresponsiveness

Cited by 2 publications

References 28 publications

Mechanisms underlying the pathogenesis of hyper-contractility of bronchial smooth muscle in allergic asthma

Mechanisms underlying the pathogenesis of hyper-contractility of bronchial smooth muscle in allergic asthma

Implications of immune-inflammatory responses in smooth muscle dysfunction and disease

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