GHRH antagonists support lung endothelial barrier function

Mohammad A. Uddin, Mohammad S. Akhter, Sitanshu S. Singh, Khadeja Tul Kubra, Andrew V. Schally, Seetharama Jois, Nektarios Barabutis

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Growth Hormone-Releasing Hormone (GHRH) regulates the release of growth hormone from the anterior pituitary gland. GHRH also acts as a growth and inflammatory factor in a variety of experimental models in oncology. In the current study, we used bovine pulmonary arterial cells in order to investigate the effects of GHRH and its antagonistic and agonistic analogs in key intracellular pathways that regulate endothelial permeability. GHRH antagonists suppressed the activation of MLC2, ERK1/2, JAK2/STAT3 pathway and increased the intracellular P53 and pAMPK levels. In contrast, both GHRH and GHRH agonist MR409 exerted the opposite effects. Furthermore, GHRH antagonists supported the integrity of endothelial barrier, while GHRH and GHRH agonists had the contrary effects, as reflected in measurements of transendothelial resistance. Our observations support the evidence for the anti–inflammatory role of GHRH antagonists in the vasculature. Moreover, our results suggest that GHRH antagonists should be considered as promising therapeutic agents for treating severe respiratory abnormalities, such as the lethal Acute Respiratory Distress Syndrome (ARDS).

Original languageEnglish (US)
Article number1669989
JournalTissue Barriers
Volume7
Issue number4
DOIs
StatePublished - Oct 2 2019

Keywords

  • Inflammation
  • P53
  • endothelial function

ASJC Scopus subject areas

  • Biochemistry
  • Histology
  • Cell Biology

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