title: Analysis of transforming growth factor β signaling in chronic rhinosinusitis.
abstract: BACKGROUND
  It has been reported that there is a significant difference in the local tissue concentration of transforming growth factor (TGF)-β1 between chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis without nasal polyps (CRSwNP) patients. TGF-β has been reported to play an important role in regulating epithelial cell repair in lower airway remodeling and may be a critical factor involved in the remodeling process of chronic rhinosinusitis (CRS).
  
  
  METHODS
  Ethmoidal mucosal samples collected from CRS and healthy control patients were analyzed for TGF-β1, TGF-β receptor I, TGF-β receptor II, Smad3, phospho-Smad3, Smad7, and Smad anchor for receptor activation by Western blotting analysis. The proliferation of sinonasal epithelial cells at baseline and after TGF-β1 and/or EGF stimulation was evaluated by the MTT assay.
  
  
  RESULTS
  In CRSsNP, TGF-β1, TGF-β receptor I, TGF-β receptor II, and Smad3 protein levels were significantly higher than controls. In CRSwNP, TGF-β1, Smad3, and pSmad3 protein levels were significantly lower than controls. Smad7 protein was significantly higher in CRS than controls. In vitro experiments demonstrated that the baseline proliferation levels of sinonasal epithelial cells were lower in CRS than controls.
  
  
  CONCLUSIONS
  CRSwNP is characterized by a lower level of TGF-signaling compared with the control. In CRSsNP, although the upstream signaling of TGF-β was enhanced, the high Smad7 protein expression may restrain the downstream signaling components (e.g., pSmad3) and the TGF-β antiproliferative effect on sinonasal epithelium. The difference in the local tissue concentration of TGF-β1 between CRSsNP and CRSwNP patients did not result in significant differences in epithelial proliferation.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China (Email: 1964liyunchuan@163.com).
authors.forename: Yun-Chuan
authors.initials: YC
authors.lastname: Li
authors.forename: Yun-Song
authors.initials: YS
authors.lastname: An
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Hong-Rui
authors.initials: HR
authors.lastname: Zang
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012852:Sinusitis / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D055815:Young Adult
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D047908:Intracellular Signaling Peptides and Proteins; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; C116420:ZFYVE16 protein, human; D012697:Serine Endopeptidases