Neurokinin-neurotrophin interactions in airway smooth muscle

Meuchel, Lucas W.; Stewart, Alecia; Smelter, Dan F.; Abcejo, Amard J.; Thompson, Michael A.; Zaidi, Syed I. A.; Martin, Richard J.; Prakash, Y. S.

doi:10.1152/ajplung.00320.2010

Cited by 22 publications

(34 citation statements)

References 59 publications

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“…Here, it appears that ASM itself can release BDNF (200,324) both at baseline and in response to inflammatory stimuli. Importantly, BDNF can nongenomically enhance ASM [Ca 2ϩ ] i (236) and potentiate the effects of receptors for neurally derived factors such as the neurokinins (200). BDNF further appears to play a role in airway remodeling (5) (see below).…”

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 86%

“…However, there are now considerable data that ASM also expresses the TrkB and TrkC receptors for BDNF/neurotrophin 4 and neurotrophin 3, respectively (200,213,236,239,268,291,345). Here, it appears that ASM itself can release BDNF (200,324) both at baseline and in response to inflammatory stimuli. Importantly, BDNF can nongenomically enhance ASM [Ca 2ϩ ] i (236) and potentiate the effects of receptors for neurally derived factors such as the neurokinins (200).…”

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

“…On the other hand, prolonged dopaminergic signaling via a D2-like, Gi-coupled pathway leads to enhancement of the Gs-coupled ␤2-adrenoceptor (␤2AR) system, thus increasing cAMP and promoting bronchodilation. GRK3, G protein-coupled receptor kinase; RGS4, G-protein signaling 4. dence for TRPV1 in nonneuronal airway cells such as epithelium (298) and ASM (354) but considerable data on the expression of kinin receptors in ASM (173,200,252,322). Thus it would be interesting to determine whether OGR1 can indirectly influence these mechanisms.…”

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

“…However, a number of recent studies have found that the Trk family of receptors (RTK class VII; Fig. 4) that are responsive to the neurotrophin family of growth factors (238) has novel, diverse roles in ASM, including enhancing [Ca 2ϩ ] i and contractility, particularly in the setting of inflammation (120,200,223,236,239,248,268,344). Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are well recognized in the nervous system for both long-term genomic effects on neuronal growth, differentiation, and survival (181), as well as nongenomic, rapid effects of enhancing [Ca 2ϩ ] i and neurotransmitter release (24,159).…”

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

“…The presumed target of the released NGF is ASM, given expression of the cognate TrkA receptors in ASM (75,213,222,238). However, there are now considerable data that ASM also expresses the TrkB and TrkC receptors for BDNF/neurotrophin 4 and neurotrophin 3, respectively (200,213,236,239,268,291,345). Here, it appears that ASM itself can release BDNF (200,324) both at baseline and in response to inflammatory stimuli.…”

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

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Airway smooth muscle in airway reactivity and remodeling: what have we learned?

Prakash

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Prakash YS. Airway smooth muscle in airway reactivity and remodeling: what have we learned? Am J Physiol Lung Cell Mol Physiol 305: L912-L933, 2013. First published October 18, 2013 doi:10.1152/ajplung.00259.2013.-It is now established that airway smooth muscle (ASM) has roles in determining airway structure and function, well beyond that as the major contractile element. Indeed, changes in ASM function are central to the manifestation of allergic, inflammatory, and fibrotic airway diseases in both children and adults, as well as to airway responses to local and environmental exposures. Emerging evidence points to novel signaling mechanisms within ASM cells of different species that serve to control diverse features, including 1) [Ca 2ϩ ]i contractility and relaxation, 2) cell proliferation and apoptosis, 3) production and modulation of extracellular components, and 4) release of pro-vs. anti-inflammatory mediators and factors that regulate immunity as well as the function of other airway cell types, such as epithelium, fibroblasts, and nerves. These diverse effects of ASM "activity" result in modulation of bronchoconstriction vs. bronchodilation relevant to airway hyperresponsiveness, airway thickening, and fibrosis that influence compliance. This perspective highlights recent discoveries that reveal the central role of ASM in this regard and helps set the stage for future research toward understanding the pathways regulating ASM and, in turn, the influence of ASM on airway structure and function. Such exploration is key to development of novel therapeutic strategies that influence the pathophysiology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis.

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Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 86%

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

Section: Asm [Ca 2ϩ ] I and Contractilitymentioning

confidence: 99%

See 3 more Smart Citations

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

Prakash

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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179

154

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Sex Steroids Influence Brain-Derived Neurotropic Factor Secretion From Human Airway Smooth Muscle Cells

et al. 2015

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Brain derived neurotropic factor (BDNF) is emerging as an important player in airway inflammation, remodeling, and hyperreactivity. Separately, there is increasing evidence that sex hormones contribute to pathophysiology in the lung. BDNF and sex steroid signaling are thought to be intricately linked in the brain. There is currently little information on BDNF and sex steroid interactions in the airway, but is relevant to understanding growth factor signaling in the context of asthma in men vs. women. In this study, we assessed the effect of sex steroids on BDNF expression and secretion in human airway smooth muscle (ASM). Human ASM was treated with estrogen (E2) or testosterone (T, 10nM each) and intracellular BDNF and secreted BDNF measured. E2 and T significantly reduced secretion of BDNF; effects prevented by estrogen and androgen receptor inhibitor, ICI 182,780 (1uM) and flutamide (10uM), respectively. Interestingly, no significant changes were observed in intracellular BDNF mRNA or protein expression. High affinity BDNF receptor, TrkB, was not altered by E2 or T. E2 (but not T) significantly increased intracellular cyclic AMP levels. Notably, Epac1 and Epac2 expression were significantly reduced by E2 and T. Furthermore, SNARE complex protein SNAP25 was decreased. Overall, these novel data suggest that physiologically relevant concentrations of E2 or T inhibit BDNF secretion in human ASM, suggesting a potential interaction of sex steroids with BDNF in the airway that is different from brain. The relevance of sex steroid-BDNF interactions may lie in their overall contribution to airway diseases such as asthma.

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