ArticleFrontiers in physiology2014
Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction.
Article in Frontiers in physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- The development of growth hormone-releasing hormone analogs: Therapeutic advances in cancer, regenerative medicine, and metabolic disorders.Reviews in endocrine & metabolic disorders · 2025Review
- GHRH in diabetes and metabolism.Reviews in endocrine & metabolic disorders · 2025Review
- Mitochondrial destabilization in tendinopathy and potential therapeutic strategies.Journal of orthopaedic translation · 2024Review
- Stimuli-Responsive Delivery Systems for Intervertebral Disc Degeneration.International journal of nanomedicine · 2024Review
- GHRH agonist MR-409 protects β-cells from streptozotocin-induced diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Multiple nano-drug delivery systems for intervertebral disc degeneration: Current status and future perspectives.Bioactive materials · 2023Review
- Growth hormone-releasing hormone antagonist MIA-602 inhibits inflammation induced by SARS-CoV-2 spike protein and bacterial lipopolysaccharide synergism in macrophages and human peripheral blood mononuclear cells.Frontiers in immunology · 2023Article
- A thermosensitive, reactive oxygen species-responsive, MR409-encapsulated hydrogel ameliorates disc degeneration in rats by inhibiting the secretory autophagy pathway.Theranostics · 2021Article
- Biomechanical Forces and Oxidative Stress: Implications for Pulmonary Vascular Disease.Antioxidants & redox signaling · 2019Review
- Regulation of Vascular Calcification by Growth Hormone-Releasing Hormone and Its Agonists.Circulation research · 2018Article
- Endothelial Cdc42 deficiency impairs endothelial regeneration and vascular repair after inflammatory vascular injury.Respiratory research · 2018Article
- Direct factor Xa inhibition attenuates acute lung injury progression via modulation of the PAR-2/NF-κB signaling pathway.American journal of translational research · 2018Article
- Method for the Culture of Mouse Pulmonary Microvascular Endothelial Cells.Scientific pages of pulmonology · 2017Article
- Beneficial effects of growth hormone-releasing hormone agonists on rat INS-1 cells and on streptozotocin-induced NOD/SCID mice.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- The Acute Respiratory Distress Syndrome: Mechanisms and Perspective Therapeutic Approaches.Austin journal of vascular medicine · 2015Article
- New therapeutic approach to heart failure due to myocardial infarction based on targeting growth hormone-releasing hormone receptor.Oncotarget · 2015Article
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
rationaleAntibiotic treatment of patients infected with G(-) or G(+) bacteria promotes release of the toxins lipopolysaccharide (LPS) and pneumolysin (PLY) in their lungs. Growth Hormone-releasing Hormone (GHRH) agonist JI-34 protects human lung microvascular endothelial cells (HL-MVEC), expressing splice variant 1 (SV-1) of the receptor, from PLY-induced barrier dysfunction. We investigated whether JI-34 also blunts LPS-induced hyperpermeability. Since GHRH receptor (GHRH-R) signaling can potentially stimulate both cAMP-dependent barrier-protective pathways as well as barrier-disruptive protein kinase C pathways, we studied their interaction in GHRH agonist-treated HL-MVEC, in the presence of PLY, by means of siRNA-mediated protein kinase A (PKA) depletion.
methodsBarrier function measurements were done in HL-MVEC monolayers using Electrical Cell substrate Impedance Sensing (ECIS) and VE-cadherin expression by Western blotting. Capillary leak was assessed by Evans Blue dye (EBD) incorporation. Cytokine generation in broncho-alveolar lavage fluid (BALF) was measured by multiplex analysis. PKA and PKC-α activity were assessed by Western blotting.
resultsGHRH agonist JI-34 significantly blunts LPS-induced barrier dysfunction, at least in part by preserving VE-cadherin expression, while not affecting inflammation. In addition to activating PKA, GHRH agonist also increases PKC-α activity in PLY-treated HL-MVEC. Treatment with PLY significantly decreases resistance in control siRNA-treated HL-MVEC, but does so even more in PKA-depleted monolayers. Pretreatment with GHRH agonist blunts PLY-induced permeability in control siRNA-treated HL-MVEC, but fails to improve barrier function in PKA-depleted PLY-treated monolayers.
conclusionsGHRH signaling in HL-MVEC protects from both LPS and PLY-mediated endothelial barrier dysfunction and concurrently induces a barrier-protective PKA-mediated and a barrier-disruptive PKC-α-induced pathway in the presence of PLY, the former of which dominates the latter.
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