title: Analysis of epidermal growth factor signaling in nasal mucosa epithelial cell proliferation involved in chronic rhinosinusitis.
abstract: BACKGROUND
  Aberrant epithelial repair has been observed in chronic rhinosinusitis (CRS) patients; however, the mechanism of epithelial cell repair regulation is unclear. Epidermal growth factor (EGF) plays an important role in regulating epithelial cell repair in lower airway and may be a critical factor in the remodeling processes of CRS. The objective of our research is to evaluate the differences between CRS and normal subjects and between chronic rhinosinusitis without nasal polys (CRSsNP) and chronic rhinosinusitis with nasal polys (CRSwNP) in the regulation of EGF pathways and the regulating proliferative position of classic Ras/Raf/MEK/ERK pathways.
  
  
  METHODS
  We evaluated the proliferation rates of ethmoidal mucosal cells before and after stimulation with EGF, epidermal growth factor receptor (EGFR) kinase inhibitor AG1478, and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 using MTT assays. We also analyzed the sinonasal epithelial cells collected from control subjects and patients with CRS subtypes CRSsNP and CRSwNP for the expression of ERK1/2, phosphorylated ERK1/2, P21, P15, and P27 using western blotting analyses.
  
  
  RESULTS
  The proliferation rates of sinonasal epithelial cells before and after EGF stimulation were lower in CRS patients than in the controls. AG1478 or PD98059 inhibitor treatment of control epithelial cells did not result in a significant difference in proliferation. Although, AG1478 and PD98059 inhibited the proliferation of CRS cells, the degree of proliferation inhibition was markedly different in CRSsNP. AG1478 suppressed the proliferation of CRSwNP epithelial cells, whereas PD98059 had no effect. The ratio of ERK1/2 phosphorylation in CRS cells was lower than that of the control cells. Cyclin-dependent kinase inhibitors were highly expressed in CRS cells compared with that of control cells. ERK1/2 and P27 showed differential expression in CRSsNP and CRSwNP.
  
  
  CONCLUSIONS
  Differences existed in EGF pathways in CRS patients and normal subjects as well as in CRSsNP and CRSwNP. Classical Ras/Raf/MEK/ERK pathway may assume absolute superiority in control cells. Ras/Raf/MEK/ERK classical pathway and other pathways might be active at the same time to stimulate epithelial cell proliferation in CRSsNP. The function of Ras/Raf/MEK/ERK classical pathway was weaker in CRSwNP than in CRSsNP and when the classical pathway was blocked in CRSwNP, some other pathway could have completely compensated the proliferation induced by the Ras/Raf/MEK/ERK pathway.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University; State Key Laboratory Otolaryngology Head and Neck Surgery of Ministry of Education, Beijing 100730, China. Email: liyunchuan_ent@163.com.
authors.forename: Yunchuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University; State Key Laboratory Otolaryngology Head and Neck Surgery of Ministry of Education, Beijing 100730, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University; State Key Laboratory Otolaryngology Head and Neck Surgery of Ministry of Education, Beijing 100730, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University; State Key Laboratory Otolaryngology Head and Neck Surgery of Ministry of Education, Beijing 100730, China.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Zang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University; State Key Laboratory Otolaryngology Head and Neck Surgery of Ministry of Education, Beijing 100730, China.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University; State Key Laboratory Otolaryngology Head and Neck Surgery of Ministry of Education, Beijing 100730, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University; State Key Laboratory Otolaryngology Head and Neck Surgery of Ministry of Education, Beijing 100730, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University; State Key Laboratory Otolaryngology Head and Neck Surgery of Ministry of Education, Beijing 100730, China.
authors.forename: Fujuan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University; State Key Laboratory Otolaryngology Head and Neck Surgery of Ministry of Education, Beijing 100730, China.
authors.forename: Yani
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology*; D012852:Sinusitis / Q000378:metabolism*
chemical_list: D004815:Epidermal Growth Factor