2018
DOI: 10.1111/cmi.12957
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FOXA2 depletion leads to mucus hypersecretion in canine airways with respiratory diseases

Abstract: Because of exposure to environmental pollutants, infectious agents, and genetic predisposition, companion animals develop respiratory illnesses similar to those in humans. Older dogs of smaller breeds develop canine infectious respiratory disease, chronic bronchitis, and chronic obstructive pulmonary disease, with chronic lung infection, airway goblet cell hyperplasia and metaplasia, and mucus hypersecretion. Excessive mucus clogs airways, reduces gas exchanges, disables the mucociliary clearance, and reduces … Show more

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Cited by 12 publications
(22 citation statements)
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“…Interestingly, MUC5B gene transcription is differentiallyregulated by FOXA2. Inhibition of FOXA2 by bacterial pathogens elevates MUC5B expression (26,(52)(53)(54). In contrast, FOXA2 positively regulates MUC5B expression in both idiopathic pulmonary fibrosis (55) and asthma (56), most likely caused by polymorphism in the MUC5B promoter (57).…”
Section: Foxa2 and Mucus Homeostasismentioning
confidence: 99%
“…Interestingly, MUC5B gene transcription is differentiallyregulated by FOXA2. Inhibition of FOXA2 by bacterial pathogens elevates MUC5B expression (26,(52)(53)(54). In contrast, FOXA2 positively regulates MUC5B expression in both idiopathic pulmonary fibrosis (55) and asthma (56), most likely caused by polymorphism in the MUC5B promoter (57).…”
Section: Foxa2 and Mucus Homeostasismentioning
confidence: 99%
“…Foxa2 is highly conserved and widely expressed during murine embryogenesis and in adult tissues, where it functions as a primary transcription factor mediating the expression of genes involved in homeostasis and defenses, especially in the lung tissues [18]. Studies report decreased levels of Foxa2 in allergic diseases and asthma [20,24]. Therefore, genes associated with defenses may be affected by the depletion of Foxa2 in allergic diseases and asthma.…”
Section: Discussionmentioning
confidence: 99%
“…Many clinical features of respiratory diseases in companion animals resemble human patients, including CB, COPD, goblet cell metaplasia and hyperplasia, mucus hypersecretion, and chronic lung infections. 35 The prevalence of blastomycosis and histoplasmosis in dogs and cats is comparable to humans. 48 Notably, geographic prevalence of canine pulmonary mycoses overlaps with that of humans, allowing it to be a potential epidemiologic marker to predict outbreaks in human.…”
mentioning
confidence: 99%
“…29 Infections by respiratory bacterial pathogens Pseudomonas aeruginosa, Mycoplasma pneumoniae, and Bordetella bronchiseptica, as well as exposure to P. aeruginosa exotoxin pyocyanin consistently reduce the expression of FOXA2 in human, mouse, and canine airways. 28,30e34 FOXA2 is also depleted in human COPD lungs 34,35 and in canine patients with naturally developed COPD and CB. 35 Imbalance among cytokine responses often plays an important role in driving and worsening airway disease pathogenesis.…”
mentioning
confidence: 99%
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