Enhanced expression of SAM-pointed domain-containing Ets-like factor in chronic rhinosinusitis with nasal polyps.
OBJECTIVE
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by significant goblet hyperplasia and mucus hypersecretion. However, the molecular mechanism underlying mucin overexpression in CRSwNP has not been well characterized. This study sought to assess the expression of SAM-pointed domain-containing Ets-like factor (SPDEF) and its regulation of mucin production in CRSwNP patients.


METHODS
Prospective laboratory-based study.


METHODS
Polyp and control nasal tissues were collected from 27 CRSwNP patients and 15 control subjects. The expression of SPDEF and MUC5AC in the nasal tissues was examined by immunohistochemistry staining, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. In addition, SPDEF and MUC5AC expression was evaluated in cultured polyp epithelial cells and bronchial epithelial cells (BECs) in the presence of proinflammatory cytokines, corticosteroids and SPDEF small interfering RNA (siRNA) using qRT-PCR and western blot analysis.


RESULTS
We found significantly increased SPDEF and MUC5AC expression in CRSwNP patients compared to the controls (P < .05); the mRNA level of SPDEF was positively correlated with MUC5AC expression in CRS patients (P < .05). There was a significant difference in SPDEF and MUC5AC expression in eosinophilic and noneosinophilic CRSwNP patients (P < .05). Interleukin (IL)-13, IL-8, and IL-17A significantly increased SPDEF and MUC5AC expression in vitro (P < .05). SPDEF siRNA significantly inhibited SPDEF and MUC5AC expression in BECs in response to IL-13, IL-8, and IL-17A (P < .05).


CONCLUSIONS
Our findings suggested that SPDEF may be regarded as a promising therapeutic target for modulating mucus hypersecretion in CRSwNP.
Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai; Department of Otolaryngology, The First People's Hospital of Foshan City, Foshan.
Jing
J
Bai
Beiping
B
Miao
Xingmei
X
Wu
Xi
X
Luo
Renqiang
R
Ma
Jia
J
Zhang
Lei
L
Li
Jianbo
J
Shi
Huabin
H
Li
D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000096:biosynthesis / Q000235:genetics*; D009298:Nasal Polyps / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D011446:Prospective Studies; D050783:Proto-Oncogene Proteins c-ets / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D012852:Sinusitis / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
C524678:MUC5AC protein, human; D055271:Mucin 5AC; D050783:Proto-Oncogene Proteins c-ets; C403974:SPDEF protein, human; D012313:RNA
Chronic rhinosinusitis; MUC5AC; SPDEF; corticosteroid; cytokine; nasal polyps; siRNA