PMID- 31665560
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 20
IP  - 3
DP  - 2020 Mar
TI  - Amphiregulin contributes to airway remodeling in chronic allograft dysfunction 
      after lung transplantation.
PG  - 825-833
LID - 10.1111/ajt.15667 [doi]
AB  - Chronic lung allograft dysfunction (CLAD), a condition of excess matrix 
      deposition and airways fibrosis, limits survival after lung transplantation. 
      Amphiregulin (Areg) is an epidermal growth factor receptor (EGFR) ligand 
      suggested to regulate airway injury and repair. We sought to determine whether 
      Areg expression increases in CLAD, localize the cellular source of Areg induction 
      in CLAD, and assess its effects on airway matrix deposition. Lung fluid Areg 
      protein was quantified in patients with or without CLAD. In situ hybridization 
      was performed to localize Areg and EGFR transcript in CLAD and normal lung 
      tissue. Expression of hyaluronan, a matrix constituent that accumulates in CLAD, 
      was measured in Areg-exposed bronchial epithelial cells in the presence or 
      absence of an EGFR inhibitor. We demonstrated that lung fluid Areg protein was 
      significantly increased in CLAD in a discovery and replication cohort. Areg and 
      EGFR transcripts were abundantly expressed within CLAD tissue, localized to 
      basally distributed airway epithelial cells overlying fibrotic regions. 
      Areg-exposed bronchial epithelial cells increased hyaluronan and hyaluronan 
      synthase expression in an EGFR-dependent manner. Collectively, these novel 
      observations suggest that Areg contributes to airway remodeling and CLAD. 
      Moreover these data implicate a role for EGFR signaling in CLAD pathogenesis, 
      suggesting novel therapeutic targets.
CI  - (c) 2019 The American Society of Transplantation and the American Society of 
      Transplant Surgeons.
FAU - Todd, Jamie L
AU  - Todd JL
AUID- ORCID: 0000-0003-4247-3693
AD  - Department of Medicine, Division of Pulmonary, Allergy and Critical Care 
      Medicine, Duke University Medical Center, Durham, North Carolina.
AD  - Duke University Medical Center, Duke Clinical Research Institute, Durham, North 
      Carolina.
FAU - Kelly, Fran L
AU  - Kelly FL
AD  - Department of Medicine, Division of Pulmonary, Allergy and Critical Care 
      Medicine, Duke University Medical Center, Durham, North Carolina.
FAU - Nagler, Andrew
AU  - Nagler A
AD  - Department of Medicine, Division of Pulmonary, Allergy and Critical Care 
      Medicine, Duke University Medical Center, Durham, North Carolina.
FAU - Banner, Kane
AU  - Banner K
AD  - Department of Medicine, Division of Pulmonary, Allergy and Critical Care 
      Medicine, Duke University Medical Center, Durham, North Carolina.
FAU - Pavlisko, Elizabeth N
AU  - Pavlisko EN
AD  - Department of Pathology, Duke University Medical Center, Durham, North Carolina.
FAU - Belperio, John A
AU  - Belperio JA
AD  - Department of Medicine, Division of Pulmonary Medicine, University of California 
      Los Angeles, Los Angeles, California.
FAU - Brass, David
AU  - Brass D
AD  - Department of Medicine, Division of Pulmonary, Allergy and Critical Care 
      Medicine, Duke University Medical Center, Durham, North Carolina.
FAU - Weigt, S Sam
AU  - Weigt SS
AD  - Department of Medicine, Division of Pulmonary Medicine, University of California 
      Los Angeles, Los Angeles, California.
FAU - Palmer, Scott M
AU  - Palmer SM
AD  - Department of Medicine, Division of Pulmonary, Allergy and Critical Care 
      Medicine, Duke University Medical Center, Durham, North Carolina.
AD  - Duke University Medical Center, Duke Clinical Research Institute, Durham, North 
      Carolina.
LA  - eng
GR  - P01 HL108793/HL/NHLBI NIH HHS/United States
GR  - P30 CA014236/CA/NCI NIH HHS/United States
GR  - K23 AI125670/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20191201
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (Amphiregulin)
SB  - IM
CIN - Am J Transplant. 2020 Mar;20(3):631-632. PMID: 31833651
MH  - *Airway Remodeling
MH  - Allografts
MH  - Amphiregulin/genetics
MH  - Humans
MH  - Lung
MH  - *Lung Transplantation/adverse effects
PMC - PMC7042065
MID - NIHMS1057045
OTO - NOTNLM
OT  - bronchiolitis obliterans (BOS)
OT  - lung transplantation/pulmonology
OT  - rejection: chronic
OT  - translational research/science
COIS- Disclosure The authors of this manuscript have no conflicts of interest to 
      disclose as described by the American Journal of Transplantation.
EDAT- 2019/10/31 06:00
MHDA- 2021/06/22 06:00
PMCR- 2021/03/01
CRDT- 2019/10/31 06:00
PHST- 2019/05/17 00:00 [received]
PHST- 2019/10/04 00:00 [revised]
PHST- 2019/10/17 00:00 [accepted]
PHST- 2019/10/31 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2019/10/31 06:00 [entrez]
PHST- 2021/03/01 00:00 [pmc-release]
AID - S1600-6135(22)22246-1 [pii]
AID - 10.1111/ajt.15667 [doi]
PST - ppublish
SO  - Am J Transplant. 2020 Mar;20(3):825-833. doi: 10.1111/ajt.15667. Epub 2019 Dec 1.