Transient Receptor Potential and Orai Channels in Airway Smooth Muscle Cells

Xiao, Junhua; Wang, Yong-Xiao; Zheng, Yun‐Min

doi:10.1007/978-3-319-01312-1_3

Cited by 8 publications

(10 citation statements)

References 56 publications

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“…These KD mice do not develop allergen‐induced airway hyperresponsiveness. These results are consistentwith the recent reports from our group and others, in which among all 7 members, TRPC3 channels exhibit a predominant functional activity in normal ASMCs and an increase in the activity and expression in AIAD ASMCs (2, 5). Our findings also provide further evidence that TRPC3 channels may play a vital role in AIAD.…”

Section: Discussionsupporting

confidence: 94%

“…Corticosteroids, β2‐adrenergic agonists, and muscarinic receptor antagonists have been used as the first‐line therapeutic drugs for treatment of asthma for several decades, However, these drugs may have significant adverse effects, such as lack of efficacy, exacerbation of asthma, and even death (1). Considering that ion channels play an essential role in ASMC contraction, scientists have made great efforts to develop novel and effective interventions targeting ion channels in the treatment of asthma; unfortunately, there has been no breakthrough so far (2, 3, 20). In this study, we demonstrate that intravenous injection of lentiviral TRPC3 channel shRNAs can sufficiently KD ASMC TRPC3 channel expression and activity in mice.…”

Section: Discussionmentioning

confidence: 99%

“…Recent in vitro studies from our laboratory and others indicate that canonical transient receptor potential 3 (TRPC3)‐encoded channels show a predominant activity in ASMCs, and the channel expression and activity are increased in ASMCs from mice with allergen‐induced airway disease (AIAD) and humans with asthma (2, 4, 5). In this study, we first addressed a fundamental question whether the in vivo knockdown (KD) or pharmacological inhibition of TRPC3 could prevent AIAD.…”

mentioning

confidence: 99%

“…The hallmark features of asthma are airway hyperresponsiveness and remodeling, which may result from increased Ca 2+ signaling in airway smooth muscle cells (ASMCs). Thus, specific interventions for Ca 2+ signaling may become novel and effective drugs for asthma (1)(2)(3).…”

mentioning

confidence: 99%

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Canonical transient receptor potential 3 channels activate NF‐κB to mediate allergic airway disease via PKC‐α/IκB‐α and calcineurin/IκB‐β pathways

et al. 2015

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The purpose of this study was to determine the role of canonical transient receptor potential 3 (TRPC3) channel in allergen-induced airway disease (AIAD) and its underlying signaling mechanisms. The procedures included (1) intravenous injection of lentiviral TRPC3 channel or nonsilencing short hairpin ribonucleic acid (shRNA) to make the channel knockdown (KD) or control mice, (2) allergen sensitization/challenge to induce AIAD, (3) patch-clamp recording and Ca(2+) imaging to examine the channel activity, and (4) gene manipulations and other methods to determine the underlying signaling mechanisms. The findings are that (1) intravenous or intranasal delivery of TRPC3 channel lentiviral shRNAs or blocker 1-[4-[(2,3,3-trichloro-1-oxo-2-propen-1-yl)amino]phenyl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid prevents AIAD in mice, (2) TRPC3 channel KD and overexpression, respectively, blocks and augments protein kinase C-α/nuclear factor of κ light polypeptide gene enhancer in B-cell inhibitor-α (PKC-α/IκB-α)-mediated or calcineurin/IκB-β-dependent, NF-κB-dependent allergen-induced airway smooth muscle cell (ASMC) hyperproliferation and cyclin D1 (an important cell proliferation molecule) induction, and (3) the changes of the major molecules of the PKC-α/IκBα- and calcineurin/IκB-β-dependent NF-κB signaling pathways are also observed in asthmatic human ASMCs. The conclusions are that TRPC3 channels plays an essential role in AIAD via the PKC-α/IκB-α- and calcineurin/IκB-β-dependent NF-κB signaling pathways, and lentiviral shRNA or inhibitor of TRPC3 channels may become novel and effective treatments for AIAD.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Canonical transient receptor potential 3 channels activate NF‐κB to mediate allergic airway disease via PKC‐α/IκB‐α and calcineurin/IκB‐β pathways

et al. 2015

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“…To further identify the NSCCs involved in TSU-68-blocked Ca 2+ influx at the molecular level, the TRPC3 inhibitor Pyr3 [44, 53] and gadolinium, which is a blocker of TRPC1, 3, 5, 6, and 7 [54], were applied sequentially. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Relaxing Effect of TSU-68, an Antiangiogenic Agent, on Mouse Airway Smooth Muscle

Tan

Lei

Lü

et al. 2017

Cell Physiol Biochem

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Background/Aims: Recently, some small-molecule compounds that were designed for cancer therapy have acquired new roles in the treatment of pulmonary diseases. However, drug screening aimed at abnormal muscle contraction is still limited. TSU-68 is a potent, orally administered, small-molecule agent that can reduce the vascular endothelial growth factor (VEGF)-induced Ca²⁺ increase in endothelial cells. We questioned whether TSU-68 could also affect calcium influx and relax airway smooth muscle (ASM) cells. The current study aimed to investigate these effects and to explore the underlying mechanisms. Methods: The effects of TSU-68 on ASM cells were studied in mice using a series of biophysiological techniques, including force measurement and patch-clamp experiments. Results: TSU-68 inhibited high K⁺ or acetylcholine chloride (ACh)-induced pre-contracted mouse tracheal rings in a concentration-dependent manner. Further research demonstrated that the TSU-68-induced ASM relaxation was mediated by calcium, which was decreased by blocking voltage-dependent Ca²⁺ channels (VDCCs) and non-selective cation channels (NSCCs). Conclusion: Our data indicated that TSU-68 relaxes tense ASM by reducing the intracellular Ca²⁺ concentration through blocking VDCCs and NSCCs, which suggested that this small molecule might be useful in the treatment of abnormal smooth muscle.

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Canonical Transient Potential Receptor-3 Channels in Normal and Diseased Airway Smooth Muscle Cells

Wang

Zheng

2019

Advances in Experimental Medicine and Biology

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Transient Receptor Potential and Orai Channels in Airway Smooth Muscle Cells

Cited by 8 publications

References 56 publications

Canonical transient receptor potential 3 channels activate NF‐κB to mediate allergic airway disease via PKC‐α/IκB‐α and calcineurin/IκB‐β pathways

Canonical transient receptor potential 3 channels activate NF‐κB to mediate allergic airway disease via PKC‐α/IκB‐α and calcineurin/IκB‐β pathways

Relaxing Effect of TSU-68, an Antiangiogenic Agent, on Mouse Airway Smooth Muscle

Canonical Transient Potential Receptor-3 Channels in Normal and Diseased Airway Smooth Muscle Cells

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