scholarly journals Smooth muscle brain‐derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma

2018 ◽  
Vol 33 (2) ◽  
pp. 3024-3034 ◽  
Author(s):  
Rodney D. Britt ◽  
Michael A. Thompson ◽  
Sarah A. Wicher ◽  
Logan J. Manlove ◽  
Anne Roesler ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Allergic Asthma ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Airway Hyperreactivity

Hyperoxia enhances brain-derived neurotrophic factor and tyrosine kinase B receptor expression in peribronchial smooth muscle of neonatal rats

2005 ◽  
Vol 289 (2) ◽  
pp. L307-L314 ◽  
Author(s):  
Qin Yao ◽  
Musa A. Haxhiu ◽  
Syed I. Zaidi ◽  
Shijian Liu ◽  
Anjum Jafri ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Airway Hyperreactivity ◽  
Receptor Expression ◽  
Postnatal Life ◽  
Bdnf Mrna ◽  
Protein Levels ◽  
Rat Pups ◽  
Hyperoxic Exposure

Airway hyperreactivity is one of the hallmarks of hyperoxic lung injury in early life. As neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are potent mediators of neuronal plasticity, we hypothesized that neurotrophin levels in the pulmonary system may be disturbed by hyperoxic exposure. We therefore evaluated the effects of hyperoxia on the expression of BDNF, NGF, and their corresponding high-affinity receptors, TrkB and TrkA, respectively, in the lung of rat pups. Five-day-old Sprague-Dawley rat pups were randomized to hyperoxic or control groups and then continuously exposed to hyperoxia (>95% oxygen) or normoxia over 7 days. At both mRNA and protein levels, BDNF was detected in lung but not in trachea; its level was substantially enhanced in lungs from the hyperoxia-exposed rat pups. Distribution of BDNF mRNA by in situ hybridization indicates that peribronchial smooth muscle was the major source of increased BDNF production in response to hyperoxic exposure. Interestingly, hyperoxia-induced elevation of BDNF was not accompanied by any changes of NGF levels in lung. Furthermore, hyperoxic exposure increased the expression of TrkB in peribronchial smooth muscle but had no effect on the distribution of the specific NGF receptor TrkA. These findings indicate that hyperoxic stress not only upregulates BDNF at mRNA and protein levels but also enhances TrkB within peribronchial smooth muscle. However, there was no corresponding effect on NGF and TrkA receptors. We speculate that the increased level of BDNF may contribute to hyperoxia-induced airway hyperresponsiveness in early postnatal life.

scholarly journals Role of brain-derived neurotrophic factor in hyperoxia-induced enhancement of contractility and impairment of relaxation in lung parenchyma

2008 ◽  
Vol 295 (2) ◽  
pp. L348-L355 ◽  
Author(s):  
Ramadan B. Sopi ◽  
Richard J. Martin ◽  
Musa A. Haxhiu ◽  
Ismail A. Dreshaj ◽  
Qin Yao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Tyrosine Kinase ◽  
Airway Smooth Muscle ◽  
Neurotrophic Factor ◽  
Critical Role ◽  
Lung Parenchyma ◽  
Brain Derived Neurotrophic Factor ◽  
Airway Hyperreactivity ◽  
Rat Pups

Prolonged hyperoxic exposure contributes to neonatal lung injury, and airway hyperreactivity is characterized by enhanced contraction and impaired relaxation of airway smooth muscle. Our previous data demonstrate that hyperoxia in rat pups upregulates expression of brain-derived neurotrophic factor (BDNF) mRNA and protein, disrupts NO-cGMP signaling, and impairs cAMP production in airway smooth muscle. We hypothesized that BDNF-tyrosine kinase B (TrkB) signaling plays a functional role in airway hyperreactivity via upregulation of cholinergic mechanisms in hyperoxia-exposed lungs. Five-day-old rat pups were exposed to ≥95% oxygen or room air for 7 days and administered daily tyrosine kinase inhibitor K-252a (50 μg·kg−1·day−1 ip) to block BDNF-TrkB signaling or vehicle. Lungs were removed for HPLC measurement of ACh or for in vitro force measurement of lung parenchymal strips. ACh content doubled in hyperoxic compared with room air-exposed lungs. K-252a treatment of hyperoxic pups restored ACh content to room air levels. Hyperoxia increased contraction and impaired relaxation of lung strips in response to incremental electrical field stimulation. K-252a administration to hyperoxic pups reversed this increase in contraction and decrease in relaxation. K-252a or TrkB-Fc was used to block the effect of exogenous BDNF in vitro. Both K-252a and TrkB-Fc blocked the effects of exogenous BDNF. Hyperoxia decreased cAMP and cGMP levels in lung strips, and blockade of BDNF-TrkB signaling restored cAMP but not cGMP to control levels. Therefore, hyperoxia-induced increase in activity of BDNF-TrkB receptor signaling appears to play a critical role in enhancing cholinergically mediated contractile responses of lung parenchyma.

scholarly journals TRPC3 regulates release of brain-derived neurotrophic factor from human airway smooth muscle

2013 ◽  
Vol 1833 (12) ◽  
pp. 2953-2960 ◽  
Author(s):  
Pawan K. Vohra ◽  
Michael A. Thompson ◽  
Venkatachalem Sathish ◽  
Alexander Kiel ◽  
Calvin Jerde ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Human Airway Smooth Muscle ◽  
Human Airway
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