PMID- 22493011
OWN - NLM
STAT- MEDLINE
DCOM- 20121130
LR  - 20211021
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 47
IP  - 3
DP  - 2012 Sep
TI  - Amphiregulin-dependent mucous cell metaplasia in a model of nonallergic lung 
      injury.
PG  - 349-57
LID - 10.1165/rcmb.2011-0257OC [doi]
AB  - Proliferation and differentiation of the pulmonary epithelium after injury is a 
      critical process in the defense against the external environment. Defects in this 
      response can result in airway remodeling, such as mucus cell metaplasia (MCM), 
      commonly seen in patients with chronic lung disease. We have previously shown 
      that amphiregulin (AREG), a ligand to the epidermal growth factor receptor 
      (EGFR), is induced during the repair/differentiation process elicited by 
      naphthalene-induced lung injury. Thus, we hypothesized that AREG signaling plays 
      an important role in epithelial proliferation and differentiation of the 
      repairing airway. Mice deficient in AREG and lung epithelial EGFR were used to 
      define roles for AREG-dependent EGFR signaling in airway repair and remodeling. 
      We show that AREG and epithelial EGFR expression is dispensable to pulmonary 
      epithelial repair after naphthalene-induced lung injury, but regulates secretory 
      cell differentiation to a mucus-producing phenotype. We show that the pulmonary 
      epithelium is the source of AREG, suggesting that naphthalene-induced MCM is 
      mediated through an autocrine signaling mechanism. However, induction of MCM 
      resulting from allergen exposure was independent of AREG. Our data demonstrate 
      that AREG-dependent EGFR signaling in airway epithelial cells contributes to MCM 
      in naphthalene-induced lung injury. We conclude that AREG may represent a 
      determinant of nonallergic chronic lung diseases complicated by MCM.
FAU - Manzo, Nicholas D
AU  - Manzo ND
AD  - Division of Pulmonary, Allergy and Critical Care, Duke University Medical Center, 
      Durham, North Carolina, USA.
FAU - Foster, W Michael
AU  - Foster WM
FAU - Stripp, Barry R
AU  - Stripp BR
LA  - eng
GR  - T32 HL007538/HL/NHLBI NIH HHS/United States
GR  - 5R01HL090146-04/HL/NHLBI NIH HHS/United States
GR  - R01 HL090146/HL/NHLBI NIH HHS/United States
GR  - 5R01ES016347/ES/NIEHS NIH HHS/United States
GR  - 5T32HL007538-27/HL/NHLBI NIH HHS/United States
GR  - R01 HL064888/HL/NHLBI NIH HHS/United States
GR  - 5R01HL064888-10/HL/NHLBI NIH HHS/United States
GR  - R01 ES016347/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120405
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Amphiregulin)
RN  - 0 (Areg protein, mouse)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Cell Differentiation
MH  - EGF Family of Proteins
MH  - ErbB Receptors/metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Glycoproteins/*physiology
MH  - Intercellular Signaling Peptides and Proteins/*physiology
MH  - Lung Injury/*pathology
MH  - Metaplasia/*pathology
MH  - Mice
MH  - Mucous Membrane/*cytology
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction/physiology
PMC - PMC3488692
EDAT- 2012/04/12 06:00
MHDA- 2012/12/10 06:00
PMCR- 2013/09/01
CRDT- 2012/04/12 06:00
PHST- 2012/04/12 06:00 [entrez]
PHST- 2012/04/12 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - rcmb.2011-0257OC [pii]
AID - 2011-0257OC [pii]
AID - 10.1165/rcmb.2011-0257OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2012 Sep;47(3):349-57. doi: 10.1165/rcmb.2011-0257OC. 
      Epub 2012 Apr 5.