Effect of secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) on airway epithelial cells

Narumoto, Osamu; Niikura, Yuichi; Ishii, Satoshi; Morihara, Hirofumi; Okashiro, Saki; Nakahari, Takashi; Nakano, Takashi; Matsumura, Hitoshi; Shimamoto, Chikao; Moriwaki, Yuji; Misawa, Hidemi; Yamashita, Naohide; Nagase, Takahide; Kawashima, Koichiro; Yamashita, Naomi

doi:10.1016/j.bbrc.2013.07.048

Cited by 17 publications

(16 citation statements)

References 34 publications

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“…The effects of low [Ca 2+ ] i on CBF in unstimulated airway ciliary cells were controversial. Kogiso et al (2017a) reported that lowering the [Ca 2+ ] i increases CBF, whereas it has been reported that lowering the [Ca 2+ ] i decreases CBF (Hayashi et al, 2005;Matsubara et al, 2007;Narumoto et al, 2013), and also that it does not change CBF (Komatani-Tamiya et al, 2012;Li et al, 2012) This suggests that PDE1 is always active at the physiological [Ca 2+ ] i in airway ciliary cells, even in patients with hypertension who take Ca 2+ channel blockers.…”

Section: Discussionmentioning

confidence: 99%

“…Kogiso et al. () reported that lowering the [Ca 2+ ] i increases CBF, whereas it has been reported that lowering the [Ca 2+ ] i decreases CBF (Hayashi et al., ; Matsubara et al., ; Narumoto et al., ), and also that it does not change CBF (Komatani‐Tamiya et al., ; Li et al., ) in the airway ciliary cells. The present study demonstrated that a change in [Ca 2+ ] i has direct and indirect actions on CBF in airway ciliary cells; lowering [Ca 2+ ] i ‘directly’ decreases CBF, whereas lowering [Ca 2+ ] i ‘indirectly’ increases CBF in a Ca 2+ ‐concentration‐dependent manner via elevation of cAMP content by inhibition of PDE1A.…”

Section: Discussionmentioning

confidence: 99%

“…However, previous studies showed that reduction of [Ca 2+ ] i induced various CBF responses in airway ciliary cells; no change (Komatani‐Tamiya et al., ; Li et al., ), a decrease (Hayashi et al., ; Matsubara et al., ; Narumoto et al., ) or an increase (Kogiso et al., , ). The Ca 2+ and cAMP signals have been recognized independently to increase CBF in nasal ciliary cells (Smith et al., ).…”

Section: Introductionmentioning

confidence: 99%

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[Ca²⁺]_i modulation of cAMP‐stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice

Kogiso

Hosogi

Ikeuchi

et al. 2018

Experimental Physiology

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What is the central question of this study? The ciliary beat frequency (CBF) of the airway is controlled by [Ca ] . However, the effects of a reduction in [Ca ] on CBF are still controversial (an increase, a decrease or no change). What is the main finding and its importance? This study demonstrated that [Ca ] directly regulates CBF (direct action) and also indirectly regulates CBF via cAMP accumulation controlled by Ca -dependent PDE1 activity (indirect action). The final CBF is determined by the balance of direct and indirect actions. PDE1 plays crucial roles in the regulation of airway CBF. ABSTRACT: [Ca ] plays crucial roles in the regulation of ciliary beat frequency (CBF) and ciliary bend angle (CBA) of airway cilia. Moreover, Ca -dependent PDE1A existing in the CBF-regulating metabolon of cilia modifies the CBF by regulating the cAMP accumulation. This study demonstrated that the CBF is regulated by a direct and an indirect action of [Ca ] ; the direct action changes CBF mediated via [Ca ] , and the indirect action changes CBF mediated via cAMP, the accumulation of which is controlled by PDE1 activity. Upon reducing [Ca ] to various levels, the direct action decreases CBF and the indirect action increases CBF. The final CBF is determined by the extent of cAMP accumulation, which is determined by the amount of inhibition of PDE1 activity, dependent on a reduction in [Ca ] ; a slight decrease induced by a nominally Ca -free solution (no cAMP accumulation via PDE1) decreases CBF, and an extreme decrease induced by 50 μm BAPTA-AM increases CBF via cAMP accumulation by inhibiting PDE1 in a similar manner to a PDE1 inhibitor (8MmIBMX). The increase in CBA in response to a reduction in [Ca ] is smaller than the increase in CBF, because no PDE1A exists in the CBA-regulating metabolon. On the contrary, an increase in [Ca ] induced by ionomycin, which decreases cAMP accumulation by PDE1A activation, caused a slower procaterol-stimulated increase in CBF than that decreased by a Ca -free solution. A decrease in [Ca ] stimulates cAMP accumulation, whereas an increase in [Ca ] inhibits cAMP accumulation in airway ciliary cells. Thus, changes in [Ca ] modulate CBF and CBA via cAMP accumulation by controlling the activity of PDE1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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[Ca²⁺]_i modulation of cAMP‐stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice

Kogiso

Hosogi

Ikeuchi

et al. 2018

Experimental Physiology

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“…The ly-6 protein, slurp-1, was initially characterized for its role in the skin disease Mal de Maleda [70,71] and is a positive regulator of α7 nAChR [72,73]. Slurp-1 lacks a GPI linkage and is one of the secreted ly-6 proteins.…”

Section: Nicotinic Allosteric Modulators and Lung Cancermentioning

confidence: 99%

Cholinergic Targets in Lung Cancer

Spindel

2016

CPD

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Background Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Methods The potential of cholinergic targets to inhibit lung cancer growth can be evaluated by use of antagonists, agonists, gene silencing and gain of function. Results Cholinergic signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Conclusions Each of these targets has their potential advantages and disadvantages for the development of new lung cancer therapies which are discussed in this review.

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“…The ly-6 protein, slurp-1 was initially characterized for its role in the skin disease Mal de Maleda [15,16] and is a positive regulator of α7 nAChR [17,18]. Slurp-1 differs from most of the ly-6 proteins as it lacks a GPI linkage and is secreted.…”

Section: Introductionmentioning

confidence: 99%

Role of Lynx1 and related Ly6 proteins as modulators of cholinergic signaling in normal and neoplastic bronchial epithelium

Song

Spindel

2015

International Immunopharmacology

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The ly-6 proteins are a large family of proteins that resemble the snake three finger alpha toxins such as α-bungarotoxin and are defined by their multiple cysteine residues. Multiple members of the ly-6 protein family can modulate nicotinic signaling including lynx1, lynx2, slurp-1, slurp-2 and prostate stem cell antigen (PSCA). Consistent with the expression of multiple nicotinic receptors in bronchial epithelium, multiple members of the nicotinic-modulatory ly-6 proteins are expressed in lung including lynx1 and lynx2. We studied the role of lynx1 as an exemplar of the role of ly-6 proteins in lung. Our data demonstrates that lynx1 acts as a negative modulator of nicotinic signaling in normal and neoplastic lung. In normal lung lynx1 serves to limit the ability of chronic nicotine exposure to increase levels of nicotinic receptors and also serves to limit the ability of nicotine to upregulate levels of GABAA receptors in lung. In turn this allows lynx1 to limit the ability of nicotine to upregulate levels of mucin which is mediated by GABAergic signaling. This suggests that lynx1- mimetics may have potential for treatment of asthma and COPD. In that most lung cancer cells also express nicotinic receptor and lynx1 we examined the role of lynx-1 in lung cancer. Lynx1 levels are decreased in lung cancers compared to adjacent normal lung. Knockdown of lynx1 by siRNAs increased growth of lung cancer cells while expression of lynx1 in lung cancer cell decreased cell proliferation. This suggests that lynx1 is an endogenous regulator of lung cancer growth. Given that multiple small molecule negative and positive allosteric modulators of nicotinic receptors have already been developed, this suggests that lynx1 is a highly druggable target both for development of drugs that may limit lung cancer growth as well as for drugs that may be effective for asthma or COPD treatment.

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Effect of secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) on airway epithelial cells

Cited by 17 publications

References 34 publications

[Ca²⁺]_i modulation of cAMP‐stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice

[Ca²⁺]_i modulation of cAMP‐stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice

Cholinergic Targets in Lung Cancer

Role of Lynx1 and related Ly6 proteins as modulators of cholinergic signaling in normal and neoplastic bronchial epithelium

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Effect of secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) on airway epithelial cells

Cited by 17 publications

References 34 publications

[Ca2+]i modulation of cAMP‐stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice

[Ca2+]i modulation of cAMP‐stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice

Cholinergic Targets in Lung Cancer

Role of Lynx1 and related Ly6 proteins as modulators of cholinergic signaling in normal and neoplastic bronchial epithelium

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[Ca²⁺]_i modulation of cAMP‐stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice

[Ca²⁺]_i modulation of cAMP‐stimulated ciliary beat frequency via PDE1 in airway ciliary cells of mice