Introduction: Chronic inflammation and tissue remodeling always occur together in chronic rhinosinusitis (CRS). Epithelial-mesenchymal transition (EMT) plays a critical role in airway remodeling. Objective: Changes of epithelial cells in sinus mucosa in different subtypes of CRS, especially in eosinophilic chronic rhinosinusitis with nasal polyps, and the role of EMT and eosinophils (EOS) in airway remodeling are still unknown. Methods: We included 85 patients in this study. They were divided into 4 groups: a normal control (NC) group, a chronic rhinosinusitis without nasal polyps (CRSsNP) group, an eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) group, and a noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group. Clinical data were all collected and analyzed. Standard hematoxylin and eosin staining, immunohistochemical staining, and 2-color immunofluorescence staining were performed. Biomarkers of EMT, epithelial cadherin, and vimentin were labeled. The immunohistochemistry results of each group were counted and statistically analyzed. Results and Conclusion: E-cadherin was downregulated, and vimentin was upregulated in epithelial tissue from the ECRSwNP group, compared with that from the control group and the other groups. The number of vimentin-expressing epithelial cells correlated with sinus CT imaging Lund-Mackay scores (r = 0.560, p < 0.001). Moreover, expression levels of vimentin in the epithelium were associated with numbers of infiltrating EOS in tissues (r = 0.710, p < 0.001) and the peripheral blood EOS ratio (r = 0.594, p < 0.001). EMT occurred in patients with CRSwNP, especially in those with ECRSwNP. Epithelial reprogramming correlates with eosinophil infiltration and disease severity. Eosinophils contributed to impairment of epithelial function and promoted EMT in CRSwNP.

1.
O’Sullivan
JA
,
Bochner
BS
.
Eosinophils and eosinophil-associated diseases: an update
.
J Allergy Clin Immunol
.
2018
;
141
(
2
):
505
17
. .
2.
Bachert
C
,
Zhang
N
,
Hellings
PW
,
Bousquet
J
.
Endotype-driven care pathways in patients with chronic rhinosinusitis
.
J Allergy Clin Immunol
.
2018
;
141
(
5
):
1543
51
. .
3.
Kennedy
DW
,
Senior
BA
,
Gannon
FH
,
Montone
KT
,
Hwang
P
,
Lanza
DC
.
Histology and histomorphometry of ethmoid bone in chronic rhinosinusitis
.
Laryngoscope
.
1998
;
108
(
4 Pt1
):
502
7
.
4.
Kagalwalla
AF
,
Akhtar
N
,
Woodruff
SA
,
Rea
BA
,
Masterson
JC
,
Mukkada
V
,
Eosinophilic esophagitis: epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment
.
J Allergy Clin Immunol
.
2012
;
129
(
5
):
1387
e7
. .
5.
Rock
JR
,
Randell
SH
,
Hogan
BL
.
Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling
.
Dis Model Mech
.
2010
;
3
(
9–10
):
545
56
. .
6.
Hupin
C
,
Gohy
S
,
Bouzin
C
,
Lecocq
M
,
Polette
M
,
Pilette
C
.
Features of mesenchymal transition in the airway epithelium from chronic rhinosinusitis
.
Allergy
.
2014
;
69
(
11
):
1540
9
. .
7.
Zhang
YV
,
Cheong
J
,
Ciapurin
N
,
McDermitt
DJ
,
Tumbar
T
.
Distinct self-renewal and differentiation phases in the niche of infrequently dividing hair follicle stem cells
.
Cell Stem Cell
.
2009
;
5
(
3
):
267
78
. .
8.
Li
CW
,
Shi
L
,
Zhang
KK
,
Li
TY
,
Lin
ZB
,
Lim
MK
,
Role of p63/p73 in epithelial remodeling and their response to steroid treatment in nasal polyposis
.
J Allergy Clin Immunol
.
2011
;
127
(
3
):
765
2
. .
9.
Yasukawa
A
,
Hosoki
K
,
Toda
M
,
Miyake
Y
,
Matsushima
Y
,
Matsumoto
T
,
Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells
.
PLoS One
.
2013
;
8
(
5
):
e64281
. .
10.
Moheimani
F
,
Roth
HM
,
Cross
J
,
Reid
AT
,
Shaheen
F
,
Warner
SM
,
Disruption of β-catenin/CBP signaling inhibits human airway epithelial-mesenchymal transition and repairβ-Catenin/CBP signaling inhibits human airway epithelial-mesenchymal transition and repair
.
Int J Biochem Cell Biol
.
2015
;
68
:
59
69
. .
11.
Park
IH
,
Kang
JH
,
Shin
JM
,
Lee
HM
.
Trichostatin A inhibits epithelial mesenchymal transition induced by TGF-β1 in airway epithelium
.
PLoS One
.
2016
;
11
(
8
):
e0162058
. .
12.
Haddad
A
,
Gaudet
M
,
Plesa
M
,
Allakhverdi
Z
,
Mogas
AK
,
Audusseau
S
,
Neutrophils from severe asthmatic patients induce epithelial to mesenchymal transition in healthy bronchial epithelial cells
.
Respir Res
.
2019
;
20
(
1
):
234
. .
13.
Dobzanski
A
,
Khalil
SM
,
Lane
AP
.
Nasal polyp fibroblasts modulate epithelial characteristics via Wnt signaling
.
Int Forum Allergy Rhinol
.
2018
;
8
(
12
):
1412
20
. .
14.
Li
X
,
Li
C
,
Zhu
G
,
Yuan
W
,
Xiao
ZA
.
TGF-β1 induces epithelial-mesenchymal transition of chronic sinusitis with nasal polyps through MicroRNA-21
.
Int Arch Allergy Immunol
.
2019
;
179
(
4
):
304
19
. .
15.
Shin
HW
,
Cho
K
,
Kim
DW
,
Han
DH
,
Khalmuratova
R
,
Kim
SW
,
Hypoxia-inducible factor 1 mediates nasal polypogenesis by inducing epithelial-to-mesenchymal transition
.
Am J Respir Crit Care Med
.
2012
;
185
(
9
):
944
54
. .
16.
Lee
M
,
Kim
DW
,
Khalmuratova
R
,
Shin
SH
,
Kim
YM
,
Han
DH
,
The IFN-γ-p38, ERK kinase axis exacerbates neutrophilic chronic rhinosinusitis by inducing the epithelial-to-mesenchymal transition
.
Mucosal Immunol
.
2019
;
12
(
3
):
601
11
. .
17.
Kainuma
K
,
Kobayashi
T
,
D’Alessandro-Gabazza
CN
,
Toda
M
,
Yasuma
T
,
Nishihama
K
,
β2 adrenergic agonist suppresses eosinophil-induced epithelial-to-mesenchymal transition of bronchial epithelial cells
.
Respir Res
.
2017
;
18
(
1
):
79
. .
18.
Fokkens
WJ
,
Lund
VJ
,
Mullol
J
,
Bachert
C
,
Alobid
I
,
Baroody
F
,
European position paper on rhinosinusitis and nasal polyps 2012
.
Rhinol Suppl
.
2012
;
23
:
3
298
. .
19.
Cao
PP
,
Li
HB
,
Wang
BF
,
Wang
SB
,
You
XJ
,
Cui
YH
,
Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese
.
J Allergy Clin Immunol
.
2009
;
124
(
3
):
478
2
. .
20.
Kang
Y
,
Massagué
J
.
Epithelial-mesenchymal transitions: twist in development and metastasis
.
Cell
.
2004
;
118
(
3
):
277
9
. .
21.
Tian
B
,
Li
X
,
Kalita
M
,
Widen
SG
,
Yang
J
,
Bhavnani
SK
,
Analysis of the TGFβ-induced program in primary airway epithelial cells shows essential role of NF-κB/RelA signaling network in type II epithelial mesenchymal transition
.
BMC Genomics
.
2015
;
16
(
1
):
529
. .
22.
Zavadil
J
,
Böttinger
EP
.
TGF-beta and epithelial-to-mesenchymal transitions
.
Oncogene
.
2005
;
24
(
37
):
5764
74
. .
23.
Zeisberg
M
,
Neilson
EG
.
Biomarkers for epithelial-mesenchymal transitions
.
J Clin Invest
.
2009
;
119
(
6
):
1429
37
. .
24.
Nawijn
MC
,
Hackett
TL
,
Postma
DS
,
van Oosterhout
AJ
,
Heijink
IH
.
E-cadherin: gatekeeper of airway mucosa and allergic sensitization
.
Trends Immunol
.
2011
;
32
(
6
):
248
55
. .
25.
Thiery
JP
,
Acloque
H
,
Huang
RY
,
Nieto
MA
.
Epithelial-mesenchymal transitions in development and disease
.
Cell
.
2009
;
139
(
5
):
871
90
. .
26.
Li
H
,
Liu
Q
,
Wang
H
,
Sun
XC
,
Yu
HP
,
Hu
L
,
Epithelial-mesenchymal transition in chronic rhinosinusitis (CRS) and the prognostic value of -SMA in postoperative outcomes of patients with CRS
.
Mol Med Rep
.
2019
;
20
(
3
):
2441
9
.
27.
Tsuda
T
,
Maeda
Y
,
Nishide
M
,
Koyama
S
,
Hayama
Y
,
Nojima
S
,
Eosinophil-derived neurotoxin enhances airway remodeling in eosinophilic chronic rhinosinusitis and correlates with disease severity
.
Int Immunol
.
2019
;
31
(
1
):
33
40
. .
28.
Könnecke
M
,
Burmeister
M
,
Pries
R
,
Böscke
R
,
Bruchhage
KL
,
Ungefroren
H
,
Epithelial-mesenchymal transition in chronic rhinosinusitis: differences revealed between epithelial cells from nasal polyps and inferior turbinates
.
Arch Immunol Ther Exp
.
2017
;
65
(
2
):
157
73
.
29.
Fujieda
S
,
Imoto
Y
,
Kato
Y
,
Ninomiya
T
,
Tokunaga
T
,
Tsutsumiuchi
T
,
Eosinophilic chronic rhinosinusitis
.
Allergol Int
.
2019
;
68
(
4
):
403
12
. .
30.
Aceves
SS
.
Remodeling and fibrosis in chronic eosinophil inflammation
.
Dig Dis
.
2014
;
32
(
1–2
):
15
21
. .
31.
Hosoki
K
,
Kainuma
K
,
Toda
M
,
Harada
E
,
Chelakkot-Govindalayathila
AL
,
Roeen
Z
,
Montelukast suppresses epithelial to mesenchymal transition of bronchial epithelial cells induced by eosinophils
.
Biochem Biophys Res Commun
.
2014
;
449
(
3
):
351
6
. .
32.
Lucendo
AJ
,
Arias
A
,
De Rezende
LC
,
Yagüe-Compadre
JL
,
Mota-Huertas
T
,
González-Castillo
S
,
Subepithelial collagen deposition, profibrogenic cytokine gene expression, and changes after prolonged fluticasone propionate treatment in adult eosinophilic esophagitis: a prospective study
.
J Allergy Clin Immunol
.
2011
;
128
(
5
):
1037
46
. .
33.
Mahmood
MQ
,
Walters
EH
,
Shukla
SD
,
Weston
S
,
Muller
HK
,
Ward
C
,
β-catenin, twist and snail: transcriptional regulation of EMT in smokers and COPD, and relation to airflow obstruction
.
Sci Rep
.
2017
;
7
(
1
):
10832
.
34.
Mahmood
MQ
,
Reid
D
,
Ward
C
,
Muller
HK
,
Knight
DA
,
Sohal
SS
,
Transforming growth factor (TGF) β1 and Smad signalling pathways: a likely key to EMT-associated COPD pathogenesis
.
Respirology
.
2017
;
22
(
1
):
133
40
.
35.
Zhuang
W
,
Li
Z
,
Dong
X
,
Zhao
N
,
Liu
Y
,
Wang
C
,
Schisandrin B inhibits TGF-β1-induced epithelial-mesenchymal transition in human A549 cells through epigenetic silencing of ZEB1
.
Exp Lung Res
.
2019
;
45
(
5–6
):
157
66
. .
36.
Evasovic
JM
,
Singer
CA
.
Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma
.
Am J Physiol Lung Cell Mol Physiol
.
2019
;
316
(
5
):
L843
68
. .
37.
Khalmuratova
R
,
Park
JW
,
Shin
HW
.
Immune cell responses and mucosal barrier disruptions in chronic rhinosinusitis
.
Immune Netw
.
2017
;
17
(
1
):
60
7
. .
38.
Zou
Y
,
Song
W
,
Zhou
L
,
Mao
Y
,
Hong
W
.
House dust mite induces Sonic hedgehog signaling that mediates epithelial-mesenchymal transition in human bronchial epithelial cells
.
Mol Med Rep
.
2019
;
20
(
5
):
4674
82
. .
39.
Johnson
JR
,
Roos
A
,
Berg
T
,
Nord
M
,
Fuxe
J
.
Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition in the large airways
.
PLoS One
.
2011
;
6
(
1
):
e16175
. .
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.