ArticleBiochimica et biophysica acta2015
cAMP-mediated secretion of brain-derived neurotrophic factor in developing airway smooth muscle.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The trial behind it
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Hydrogen sulfide alleviates hyperoxia effects on mitochondria in human developing airway smooth muscle.JCI insight · 2026Article
- A cocktail hydrogel promoting the functional interneurons regeneration of human neural progenitor cells for brain injury therapy.Journal of advanced research · 2026Article
- Indole-3-Carbinol and Its Derivatives as Neuroprotective Modulators.Brain sciences · 2024Review
- Review
- Calcium-sensing receptor and CPAP-induced neonatal airway hyperreactivity in mice.Pediatric research · 2022Article
- Calcium-Sensing Receptor Contributes to Hyperoxia Effects on Human Fetal Airway Smooth Muscle.Frontiers in physiology · 2021Article
- Hyperoxia-induced Cellular Senescence in Fetal Airway Smooth Muscle Cells.American journal of respiratory cell and molecular biology · 2019Article
- Smooth muscle brain-derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Uncovering the mechanism of Maxing Ganshi Decoction on asthma from a systematic perspective: A network pharmacology study.Scientific reports · 2018Article
- Insights into exchange factor directly activated by cAMP (EPAC) as potential target for cancer treatment.Molecular and cellular biochemistry · 2018Review
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Dibutyryl Cyclic Adenosine Monophosphate Rescues the Neurons From Degeneration in Stab Wound and Excitotoxic Injury Models.Frontiers in neuroscience · 2018Article
- Matrine Treatment Blocks NogoA-Induced Neural Inhibitory Signaling Pathway in Ongoing Experimental Autoimmune Encephalomyelitis.Molecular neurobiology · 2017Article
- Article
- Mechanisms and regulation of neurotrophin synthesis and secretion.Neurosciences (Riyadh, Saudi Arabia) · 2016Review
- Mechanisms of BDNF regulation in asthmatic airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Sex Steroids Influence Brain-Derived Neurotropic Factor Secretion From Human Airway Smooth Muscle Cells.Journal of cellular physiology · 2016Article
- Soluble guanylate cyclase modulators blunt hyperoxia effects on calcium responses of developing human airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2015Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Moderate hyperoxic exposure in preterm infants contributes to subsequent airway dysfunction and to risk of developing recurrent wheeze and asthma. The regulatory mechanisms that can contribute to hyperoxia-induced airway dysfunction are still under investigation. Recent studies in mice show that hyperoxia increases brain-derived neurotrophic factor (BDNF), a growth factor that increases airway smooth muscle (ASM) proliferation and contractility. We assessed the mechanisms underlying effects of moderate hyperoxia (50% O2) on BDNF expression and secretion in developing human ASM. Hyperoxia increased BDNF secretion, but did not alter endogenous BDNF mRNA or intracellular protein levels. Exposure to hyperoxia significantly increased [Ca2+]i responses to histamine, an effect blunted by the BDNF chelator TrkB-Fc. Hyperoxia also increased ASM cAMP levels, associated with reduced PDE4 activity, but did not alter protein kinase A (PKA) activity or adenylyl cyclase mRNA levels. However, 50% O2 increased expression of Epac2, which is activated by cAMP and can regulate protein secretion. Silencing RNA studies indicated that Epac2, but not Epac1, is important for hyperoxia-induced BDNF secretion, while PKA inhibition did not influence BDNF secretion. In turn, BDNF had autocrine effects of enhancing ASM cAMP levels, an effect inhibited by TrkB and BDNF siRNAs. Together, these novel studies suggest that hyperoxia can modulate BDNF secretion, via cAMP-mediated Epac2 activation in ASM, resulting in a positive feedback effect of BDNF-mediated elevation in cAMP levels. The potential functional role of this pathway is to sustain BDNF secretion following hyperoxic stimulus, leading to enhanced ASM contractility and proliferation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.