PMID- 27709733
OWN - NLM
STAT- MEDLINE
DCOM- 20171219
LR  - 20240213
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 35
IP  - 3
DP  - 2017 Mar
TI  - EGF-Amphiregulin Interplay in Airway Stem/Progenitor Cells Links the Pathogenesis 
      of Smoking-Induced Lesions in the Human Airway Epithelium.
PG  - 824-837
LID - 10.1002/stem.2512 [doi]
AB  - The airway epithelium of cigarette smokers undergoes dramatic remodeling with 
      hyperplasia of basal cells (BC) and mucus-producing cells, squamous metaplasia, 
      altered ciliated cell differentiation and decreased junctional barrier integrity, 
      relevant to chronic obstructive pulmonary disease and lung cancer. In this study, 
      we show that epidermal growth factor receptor (EGFR) ligand amphiregulin (AREG) 
      is induced by smoking in human airway epithelium as a result of epidermal growth 
      factor (EGF)-driven squamous differentiation of airway BC stem/progenitor cells. 
      In turn, AREG induced a unique EGFR activation pattern in human airway BC, 
      distinct from that evoked by EGF, leading to BC- and mucous hyperplasia, altered 
      ciliated cell differentiation and impaired barrier integrity. Further, AREG 
      promoted its own expression and suppressed expression of EGF, establishing an 
      autonomous self-amplifying signaling loop in airway BC relevant for promotion of 
      EGF-independent hyperplastic phenotypes. Thus, EGF-AREG interplay in airway BC 
      stem/progenitor cells is one of the mechanisms that mediates the interconnected 
      pathogenesis of all major smoking-induced lesions in the human airway epithelium. 
      Stem Cells 2017;35:824-837.
CI  - (c) 2016 AlphaMed Press.
FAU - Zuo, Wu-Lin
AU  - Zuo WL
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York, USA.
FAU - Yang, Jing
AU  - Yang J
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York, USA.
FAU - Gomi, Kazunori
AU  - Gomi K
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York, USA.
FAU - Chao, IonWa
AU  - Chao I
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York, USA.
FAU - Crystal, Ronald G
AU  - Crystal RG
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York, USA.
FAU - Shaykhiev, Renat
AU  - Shaykhiev R
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York, USA.
LA  - eng
GR  - R01 HL118541/HL/NHLBI NIH HHS/United States
GR  - UL1 RR024143/RR/NCRR NIH HHS/United States
GR  - R01 HL127393/HL/NHLBI NIH HHS/United States
GR  - R01 HL123544/HL/NHLBI NIH HHS/United States
GR  - R01 HL107882/HL/NHLBI NIH HHS/United States
GR  - UL1 TR000457/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20161117
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Amphiregulin)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Adult
MH  - Airway Remodeling
MH  - Amphiregulin/*metabolism
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cilia/metabolism
MH  - Down-Regulation
MH  - Epidermal Growth Factor/*metabolism
MH  - ErbB Receptors/metabolism
MH  - Female
MH  - Humans
MH  - Hyperplasia
MH  - Male
MH  - Respiratory Mucosa/*pathology
MH  - Smoking/*adverse effects
MH  - Stem Cells/metabolism/*pathology
MH  - Up-Regulation
PMC - PMC5330845
MID - NIHMS840598
OTO - NOTNLM
OT  - Airway basal cells
OT  - Chronic obstructive pulmonary disease
OT  - Epidermal growth factor receptor
OT  - Hyperplasia
OT  - Metaplasia
COIS- Disclosure of Potential Conflict of Interest The authors indicate no potential 
      conflicts of interest.
EDAT- 2016/10/07 06:00
MHDA- 2017/12/20 06:00
PMCR- 2017/03/01
CRDT- 2016/10/07 06:00
PHST- 2016/01/31 00:00 [received]
PHST- 2016/08/16 00:00 [revised]
PHST- 2016/09/08 00:00 [accepted]
PHST- 2016/10/07 06:00 [pubmed]
PHST- 2017/12/20 06:00 [medline]
PHST- 2016/10/07 06:00 [entrez]
PHST- 2017/03/01 00:00 [pmc-release]
AID - 10.1002/stem.2512 [doi]
PST - ppublish
SO  - Stem Cells. 2017 Mar;35(3):824-837. doi: 10.1002/stem.2512. Epub 2016 Nov 17.