title: Differential Expression and Release of Activin A and Follistatin in Chronic Rhinosinusitis with and without Nasal Polyps.
abstract: BACKGROUND
  Chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP) should be regarded as distinct clinical entities based on differential inflammatory mediator and remodeling profiles. Activin A, a member of the TGF-β superfamily, plays an important role in inflammation and remodeling in the lower airways, although its expression and release in the upper airways remain undescribed.
  
  
  OBJECTIVE
  To investigate the expression of activin A and its inhibitor follistatin in nasal tissue samples from CRSsNP and CRSwNP patients, and to monitor the spontaneous release of these molecules in a human mucosal model.
  
  
  METHODS
  Protein levels were determined using ELISA for activin A, follistatin, TGF-β1 and indicator proteins (IL-5, ECP, IFNγ) in 13 CRSsNP, 23 CRSwNP, and 10 control samples. The spontaneous release rate and the release ratios of activin A, follistatin and TGF-β1 were determined in 9 CRSsNP and 7 CRSwNP tissue fragments cultured ex-vivo. The induction of activin A and TGF-β1 by one another was studied in 7 CRSsNP tissue fragments cultured ex-vivo.
  
  
  RESULTS
  Significantly higher concentrations of activin A, follistatin, TGF-β1, and IFNγ were observed in CRSsNP compared with CRSwNP samples, whereas the concentrations of IL-5 and ECP were significantly lower. Follistatin was positively and linearly correlated with activin A in CRSsNP and CRSwNP. Activin A, follistatin and TGF-β1 were all spontaneously released by the samples, although the relative ratios released by tissue fragments from CRSsNP and CRSwNP samples were significantly different, with a higher follistatin/activin A-ratio and a follistatin/TGFß1-ratio (with less overall TGF-β1) in CRSwNP than in CRSsNP. Furthermore, TGF-β1 enhanced activin A secretion in CRSsNP tissue fragments cultured ex-vivo.
  
  
  CONCLUSIONS
  The differences in tissue concentrations and spontaneous release rates for activin A and follistatin in different CRS samples support the hypothesis that CRSsNP and CRSwNP are two distinct disease entities with respect to remodeling patterns.
authors.affiliation: Department of Otorhinolaryngology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium.
authors.forename: Koen Van
authors.initials: KV
authors.lastname: Crombruggen
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium.
authors.forename: Feng
authors.initials: F
authors.lastname: Lan
authors.affiliation: Department of Otorhinolaryngology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Otorhinolaryngology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Suling
authors.initials: S
authors.lastname: Hong
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium; Division of Nose, Throat and Ear Diseases, Clintec, Karolinska Institute, Stockholm, Sweden.
authors.forename: Claus
authors.initials: C
authors.lastname: Bachert
mesh_terms: D028341:Activins / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D038681:Follistatin / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000378:metabolism*; D012852:Sinusitis / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult; D000099222:betaIG-H3 Protein
chemical_list: D028341:Activins; D016326:Extracellular Matrix Proteins; D038681:Follistatin; D007371:Interferon-gamma; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C422405:activin A