PMID- 29540993
OWN - NLM
STAT- MEDLINE
DCOM- 20180904
LR  - 20181202
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2018
DP  - 2018
TI  - The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis 
      Lung Pathology.
PG  - 1067134
LID - 10.1155/2018/1067134 [doi]
LID - 1067134
AB  - Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) share 
      molecular mechanisms that cause the pathological symptoms they have in common. 
      Here, we review evidence suggesting that hyperactivity of the EGFR/ADAM17 axis 
      plays a role in the development of chronic lung disease in both CF and COPD. The 
      ubiquitous transmembrane protease A disintegrin and metalloprotease 17 (ADAM17) 
      forms a functional unit with the EGF receptor (EGFR), in a feedback loop 
      interaction labeled the ADAM17/EGFR axis. In airway epithelial cells, ADAM17 
      sheds multiple soluble signaling proteins by proteolysis, including EGFR ligands 
      such as amphiregulin (AREG), and proinflammatory mediators such as the 
      interleukin 6 coreceptor (IL-6R). This activity can be enhanced by injury, 
      toxins, and receptor-mediated external triggers. In addition to intracellular 
      kinases, the extracellular glutathione-dependent redox potential controls ADAM17 
      shedding. Thus, the epithelial ADAM17/EGFR axis serves as a receptor of incoming 
      luminal stress signals, relaying these to neighboring and underlying cells, which 
      plays an important role in the resolution of lung injury and inflammation. We 
      review evidence that congenital CFTR deficiency in CF and reduced CFTR activity 
      in chronic COPD may cause enhanced ADAM17/EGFR signaling through a defect in 
      glutathione secretion. In future studies, these complex interactions and the 
      options for pharmaceutical interventions will be further investigated.
FAU - Stolarczyk, Marta
AU  - Stolarczyk M
AD  - Cell Biology, Erasmus MC, Rotterdam, Netherlands.
FAU - Scholte, Bob J
AU  - Scholte BJ
AUID- ORCID: 0000-0003-3480-6494
AD  - Cell Biology, Erasmus MC, Rotterdam, Netherlands.
AD  - Pediatric Pulmonology, Erasmus MC, Rotterdam, Netherlands.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180109
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.4.24.86 (ADAM17 Protein)
SB  - IM
MH  - ADAM17 Protein/*metabolism
MH  - Animals
MH  - Cystic Fibrosis/*metabolism/pathology
MH  - ErbB Receptors/*metabolism
MH  - Humans
MH  - Lung/metabolism/pathology
MH  - Pulmonary Disease, Chronic Obstructive/*metabolism/pathology
PMC - PMC5818912
EDAT- 2018/03/16 06:00
MHDA- 2018/09/05 06:00
PMCR- 2018/01/09
CRDT- 2018/03/16 06:00
PHST- 2017/06/02 00:00 [received]
PHST- 2017/10/09 00:00 [revised]
PHST- 2017/10/23 00:00 [accepted]
PHST- 2018/03/16 06:00 [entrez]
PHST- 2018/03/16 06:00 [pubmed]
PHST- 2018/09/05 06:00 [medline]
PHST- 2018/01/09 00:00 [pmc-release]
AID - 10.1155/2018/1067134 [doi]
PST - epublish
SO  - Mediators Inflamm. 2018 Jan 9;2018:1067134. doi: 10.1155/2018/1067134. 
      eCollection 2018.