title: Differential association of MUC5AC and CLCA1 expression in small cartilaginous airways of RAO-affected and control horses.
abstract: BACKGROUND
  Airway mucus accumulation is associated with indoor irritant and allergen exposure in horses with recurrent airway obstruction (RAO). Epidermal growth factor receptor (EGFR) and a chloride channel (calcium activated, family member 1; CLCA1) are key signalling molecules involved in mucin gene expression.
  
  
  OBJECTIVE
  We hypothesised that exposure to irritants and aeroallergens would lead to increased expression of the mucin gene eqMUC5AC and increased stored mucosubstance in the airways of RAO-affected horses, associated with increased neutrophils and CLCA1 and EGFR mRNA levels.
  
  
  METHODS
  We performed quantitative RT-PCR of eqMUC5AC, CLCA1 and EGFR; volume density measurements of intraepithelial mucosubstances; and cytological differentiation of intraluminal inflammatory cells in small cartilaginous airways from cranial left and right and caudal left and right lung lobes of 5 clinically healthy and 5 RAO-affected horses that had been exposed to indoor stable environment for 5 days before euthanasia.
  
  
  RESULTS
  Neutrophils were increased in RAO-affected horses compared to clinically healthy controls. EqMUC5AC mRNA levels were positively correlated with both CLCA1 and EGFR mRNA levels in RAO-affected horses but only with CLCA1 in controls. The relationship between eqMUC5AC and CLCA1 differed in the 2 groups of horses with RAO-affected animals overexpressing CLCA1 in relation to eqMUC5AC.
  
  
  CONCLUSIONS
  These data implicate CLCA1 as a signalling molecule in the expression of eqMUC5AC in horses but also suggest differential regulation by CLCA1 and EGFR between horses with RAO and those with milder degrees of airway inflammation.
authors.affiliation: Equine Clinic, Department of Veterinary Clinical Sciences, Vetsuisse-Faculty, University of Berne, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Gerber
authors.forename: H
authors.initials: H
authors.lastname: De Feijter-Rupp
authors.forename: J
authors.initials: J
authors.lastname: Wagner
authors.forename: P
authors.initials: P
authors.lastname: Venta
authors.forename: J R
authors.initials: JR
authors.lastname: Harkema
authors.forename: N E
authors.initials: NE
authors.lastname: Robinson
mesh_terms: D000402:Airway Obstruction / Q000662:veterinary*; D000818:Animals; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005820:Genetic Testing; D006734:Horse Diseases / Q000235:genetics* / Q000378:metabolism*; D006736:Horses; D008297:Male; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary
chemical_list: D018118:Chloride Channels; D055271:Mucin 5AC