The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity

Reznikov, Leah R.; Meyerholz, David K.; Alaiwa, Mahmoud H. Abou; Kuan, Shin‐Ping; Liao, Yan‐Shin; Bormann, Nicholas L.; Bair, Thomas B.; Price, Margaret P.; Stoltz, David A.; Welsh, Michael J.

doi:10.1152/ajplung.00557.2017

Cited by 13 publications

(16 citation statements)

References 93 publications

(124 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this, a critical role for afferent and efferent airway nerves in the manifestation of asthma features has been increasingly established (6,55,56,62,63). Specific afferent contributors include the transient receptor potential vanilloid 1 (TRPV1) (65), the acid-sensing ion channel (ASIC) 1a (55), the sodium voltagegated ␣-subunit 10 (scn10a/Nav1.8) (63), and the transient receptor potential cation channel, subfamily A, member 1 (TRPA1) (10). A major efferent contributor is cholinergic transmission (56).…”

Section: Introductionmentioning

confidence: 67%

“…For example, using an adult guinea pig model of gastroesophageal reflux, Hamamoto et al (27) found that esophageal acid caused release of substance P in the lung. Consistent with this, a critical role for afferent and efferent airway nerves in the manifestation of asthma features has been increasingly established (6,55,56,62,63). Specific afferent contributors include the transient receptor potential vanilloid 1 (TRPV1) (65), the acid-sensing ion channel (ASIC) 1a (55), the sodium voltagegated ␣-subunit 10 (scn10a/Nav1.8) (63), and the transient receptor potential cation channel, subfamily A, member 1 (TRPA1) (10).…”

Section: Introductionmentioning

confidence: 89%

“…The threshold for calling significantly differentially expressed genes was set at FDR 0.05 with the average FPKM for at least one of each comparison group being higher than 0. Additional criteria using P Ͻ 0.05 were also implemented (55).…”

Section: Methodsmentioning

confidence: 99%

“…Tissues collected for RNA sequencing were from three separate experiments, consisting of both sexes, with one saline and one acid-treated animal per sex per experiment. An n of 3 was selected on the basis of our previous data (55). Our previous work for histological scoring indicated an n of 8 was required to achieve statistical significance (56); therefore, we planned for one additional animal per group.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Sex-specific airway hyperreactivity and sex-specific transcriptome remodeling in neonatal piglets challenged with intra-airway acid

Reznikov

Liao

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

Acute airway acidification is a potent stimulus of sensory nerves and occurs commonly with gastroesophageal reflux disease, cystic fibrosis, and asthma. In infants and adults, airway acidification can acutely precipitate asthma-like symptoms, and treatment-resistant asthma can be associated with gastroesophageal reflux disease. Airway protective behaviors, such as mucus secretion and airway smooth muscle contraction, are often exaggerated in asthma. These behaviors are manifested through activation of neural circuits. In some populations, the neural response to acid might be particularly important. For example, the immune response in infants is relatively immature compared with adults. Infants also have a high frequency of gastroesophageal reflux. Thus, in the current study, we compared the transcriptomes of an airway-nervous system circuit (e.g., tracheal epithelia, nodose ganglia, and brain stem) in neonatal piglets challenged with intra-airway acid. We hypothesized that the identification of parallel changes in the transcriptomes of two neutrally connected tissues might reveal the circuit response, and, hence, molecules important for the manifestation of asthma-like features. Intra-airway acid induced airway hyperreactivity and airway obstruction in male piglets. In contrast, female piglets displayed airway obstruction without airway hyperreactivity. Pairwise comparisons revealed parallel changes in genes directly implicated in airway hyperreactivity ( scn10a) in male acid-challenged piglets, whereas acid-challenged females exhibited parallel changes in genes associated with mild asthma ( stat 1 and isg15). These findings reveal sex-specific responses to acute airway acidification and highlight distinct molecules within a neural circuit that might be critical for the manifestation of asthma-like symptoms in pediatric populations.

show abstract

Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Sex-specific airway hyperreactivity and sex-specific transcriptome remodeling in neonatal piglets challenged with intra-airway acid

Reznikov

Liao

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

show abstract

“…pPCLS were made as previously described (Reznikov, Meyerholz, Abou Alaiwa, et al, 2018). Briefly, the porpoise lobe was dissected, cannulated, and insufflated with 2% (weight/vol) low‐melting‐point agarose (Invitrogen) in the culture medium.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway

et al. 2021

Self Cite

View full text Add to dashboard Cite

Substance P (SP) is a tachykinin that regulates airway mucous secretion in both health and disease. Our study aimed to determine whether overexpression of SP without pre‐existing inflammation was sufficient to induce changes in mucin secretion and transport in small airways. Utilizing porcine precision‐cut lung slices, we measured the impact of AAV‐mediated overexpression of SP on airway physiology ex vivo. Immunofluorescence signal intensity for MUC5AC was significantly increased in SP‐overexpressed precision‐cut lung slices compared to GFP controls. No difference in MUC5B signal intensity between treatments was detected. SP‐overexpressed precision‐cut lung slices also exhibited decreased IL10 mRNA, an important inhibitor of mucous cell metaplasia. Overt deficits in mucociliary transport were not noted, though a trend for decreased mean transport speed was detected in methacholine‐challenged airways overexpressing SP compared to GFP controls. Pharmacologic inhibition of the NF‐kβ pathway abrogated the effects of overexpression of SP on both MUC5AC and IL10. Collectively, these data suggest that overexpression of SP in the absence of existing inflammation increases MUC5AC via activation of the NF‐kβ pathway. Thus, these data further highlight SP as a key driver of abnormal mucous secretion and underscore NF‐kβ signaling as a pathway of potential therapeutic intervention.

show abstract

Flavokavains A- and B-Free Kava Enhances Resilience against the Adverse Health Effects of Tobacco Smoke in Mice

Bian,

Lynch,

Ballas

et al. 2024

ACS Pharmacol. Transl. Sci.

View full text Add to dashboard Cite

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onset of numerous preventive diseases and imposing significant health burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco-smoking-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use. To understand the scope of its benefits in damage reduction and potential limitations, this study evaluated the effects of AB-free kava on a panel of health indicators in mice exposed to 2–4 weeks of daily tobacco smoke exposure. Our assessments included global transcriptional profiling of the lung and liver tissues, analysis of lung inflammation, evaluation of lung function, exploration of tobacco nicotine withdrawal, and characterization of the causal protein kinase A (PKA) signaling pathway. As expected, tobacco smoke exposure perturbed a wide range of biological processes and compromised multiple functions in mice. Remarkably, AB-free kava demonstrated the ability to globally mitigate tobacco smoke-induced deficits at the molecular and functional levels with promising safety profiles, offering AB-free kava unique promise to mitigate tobacco smoke-related health damages. Further preclinical evaluations are warranted to fully harness the potential of AB-free kava in combating tobacco smoke-related harms in the preparation of its clinical translation.

show abstract

The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity

Cited by 13 publications

References 93 publications

Sex-specific airway hyperreactivity and sex-specific transcriptome remodeling in neonatal piglets challenged with intra-airway acid

Sex-specific airway hyperreactivity and sex-specific transcriptome remodeling in neonatal piglets challenged with intra-airway acid

Overexpression of Substance P in pig airways increases MUC5AC through an NF‐kβ pathway

Flavokavains A- and B-Free Kava Enhances Resilience against the Adverse Health Effects of Tobacco Smoke in Mice

Contact Info

Product

Resources

About