Involvement of the unfolded protein response in the protective effects of growth hormone releasing hormone antagonists in the lungs.
Endothelium
Inflammation
Lung injury
P53
Vascular barrier
Journal
Journal of cell communication and signaling
ISSN: 1873-9601
Titre abrégé: J Cell Commun Signal
Pays: Netherlands
ID NLM: 101308338
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
27
10
2020
accepted:
01
11
2020
pubmed:
14
11
2020
medline:
14
11
2020
entrez:
13
11
2020
Statut:
ppublish
Résumé
Growth hormone releasing hormone (GHRH) antagonists enhance endothelial barrier function and counteract the LPS-induced lung endothelial hyperpermeability, the cardinal feature of the acute respiratory distress syndrome (ARDS). The unfolded protein response (UPR) is a multifaceted molecular mechanism, strongly involved in tissue defense against injury. The current study introduces the induction of UPR by GHRH antagonists, since those peptides induced several UPR activation markers, including the inositol-requiring enzyme-1α (IRE1α), the protein kinase RNA-like ER kinase (PERK), and the activating transcription factor 6 (ATF6). On the other hand, the GHRH agonist MR-409 exerted the opposite effects. Furthermore, GHRH antagonists counteracted the kifunensine (UPR suppressor)-induced lung endothelial barrier dysfunction. Our observations suggest that UPR mediates, at least in part, the protective effects of GHRH antagonists in the lung microvasculature. To the best of our knowledge; this is the first study to provide experimental evidence in support of the hypothesis that UPR induction is a novel mechanism by which GHRH antagonists oppose severe human disease, including ARDS.
Identifiants
pubmed: 33185812
doi: 10.1007/s12079-020-00593-0
pii: 10.1007/s12079-020-00593-0
pmc: PMC7661822
doi:
Types de publication
Journal Article
Langues
eng
Pagination
125-129Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103424
Pays : United States
Organisme : NIGMS NIH HHS
ID : 5 P20 GM103424-15
Pays : United States
Organisme : Louisiana Board of Regents
ID : LEQSF(2019-22)-RD-A-26
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