Involvement of ATF6 in Octreotide-Induced Endothelial Barrier Enhancement.

: Endothelial hyperpermeability is the hallmark of severe disease, including sepsis and acute respiratory syndrome (ARDS). The development of medical countermeasures to treat the corresponding illness is of utmost importance. Synthetic somatostatin analogs (SSA) are FDA-approved drugs prescribed in patients with neuroendocrine tumors, and they act via growth hormone (GH) suppression.

Unfolded protein response modulates the effects of GHRH antagonists in experimental models of and lung injury.

The development of efficient targeted therapies to ameliorate endothelial disorders is of the utmost need, as evident by the devastating outcomes of the recent pandemic. Recent findings suggest that unfolded protein response (UPR) modulates barrier function. In the current study, we reveal that the aforementioned highly conservative mechanism is involved in the protective effects of growth hormone-releasing hormone antagonists (GHRHAnt) in lung injury, both and .

Ceapin-A7 suppresses the protective effects of Octreotide in human and bovine lung endothelial cells.

Endothelial injury can be the cause and consequence of severe inflammation and injury. Synthetic somatostatin analogs-which suppress Growth Hormone-are clinically-approved drugs associated with anti-inflammatory activities. In the present study, we suggest that the protective activities of Octreotide in human and bovine endothelial cells are mitigated by Ceapin-A7, which is an activating transcription factor 6 inhibitor.

Alleviation of LPS-induced Endothelial Injury due to GHRH Antagonist Treatment.

Background: GHRH is produced in the hypothalamus and affects various tissues beyond the pituitary, including the lungs. GHRH antagonists exert anti-inflammatory properties in several experimental models of disease, but their role inprotecting the endothelial barrier during inflammation is less understood. This study investigates the effects ofGHRHAnt on LPS-induced endothelial dysfunction.

The emerging role of Never-in-Mitosis A - Related Kinases in the endothelium.

The endothelium forms a monolayer, which functions to ensure tissue homeostasis. Barrier hyperpermeability has been associated with lung, brain and eye disease. An emerging body of evidence reports the involvement of Never-in-Mitosis A - Related Kinases in vascular responses, suggesting their value as potential therapeutic targets in endothelial-dependent disorders.

Endothelial Unfolded Protein Response-Mediated Cytoskeletal Effects.

The endothelial semipermeable monolayers ensure tissue homeostasis, are subjected to a plethora of stimuli, and their function depends on cytoskeletal integrity and remodeling. The permeability of those membranes can fluctuate to maintain organ homeostasis. In cases of severe injury, inflammation or disease, barrier hyperpermeability can cause irreparable damage of endothelium-dependent issues, and eventually death.

Growth hormone - releasing hormone in the immune system.

GHRH is a neuropeptide associated with a diverse variety of activities in human physiology and immune responses. The present study reviews the latest information on the involvement of GHRH in the immune system and inflammation, suggesting that GHRH antagonists may deliver a new therapeutic possibility in disorders related to immune system dysfunction and inflammation.

NEK-mediated barrier regulation.

Endothelial dysfunction has been associated with devastating outcomes which can eventually lead to permanent disability and death. Elucidation of the meticulously devised network orchestrating endothelial responses, provides information to develop new therapies towards endothelial-related disorders. NEK kinases - which have been involved in the development of human disease - promote vascular leak; suggesting the possibility that their inhibition may ameliorate medical conditions related to barrier derangement.

Protective Activities of Growth Hormone-Releasing Hormone Antagonists against Toxin-Induced Endothelial Injury.

GHRH regulates the secretion of GH from the anterior pituitary gland, previously associated with cancer progression and inflammation. An emerging body of evidence suggests that GHRHAnt support endothelial barrier function, but the mechanisms mediating these events are not completely understood. In the present study, it is demonstrated that the GHRHAnt JV-1-36 counteracts barrier dysfunction due to LPS or LTA treatment in HUVECs, utilizing the Dextran-FITC assay.

Protective effects of growth hormone - releasing hormone antagonists in the lungs of septic mice.

Growth hormone-releasing hormone antagonists (GHRHAnt) have been associated with antitumor and antioxidative activities. The present study investigates for the first time the effects of those compounds towards pro-inflammatory cytokine expression in a murine model of cecal ligation and puncture (CLP) - induced sepsis. The results indicate that GHRHAnt JV-1-36 significantly suppressed IL-1α, IL-6, and pSTAT3 activation in septic lungs.

Involvement of NEK2 and NEK9 in LPS - induced endothelial barrier dysfunction.

Endothelial hyperpermeability is the hallmark of severe lung injury, including acute respiratory distress syndrome. Despite the fact that Never In Mitosis A (NIMA)-related kinase 2 (NEK2) and NEK9 mediate fundamental cellular processes, our knowledge on their role in barrier function is limited. Herein we show that NEK2 and NEK9 inhibition suppresses LPS-induced paracellular hyperpermeability and myosin light chain 2 activation in endothelial cells.

Growth hormone-releasing hormone antagonists counteract interferon-γ - induced barrier dysfunction in bovine and human endothelial cells.

GHRH regulates the secretion of GH from the anterior pituitary gland. An emerging body of evidence suggests that the activities of that neuropeptide are not limited to the GH/IGF-I axis, but they expand towards the mediation of inflammatory processes. GHRHAnt were developed to oppose the activities of GHRH in malignancies, and have been associated with strong anti-inflammatory and anti-oxidative effects in a diverse variety of tissues, including the lungs.

Pneumonic Injury and Repair: A Synopsis.

It has been my great pleasure to have joined forces with editorial team in order to organize and publish a Special Issue on "Lung Injury and Repair" [...

Unfolded protein response suppression potentiates LPS-induced barrier dysfunction and inflammation in bovine pulmonary artery endothelial cells.

The development of novel strategies to counteract diseases related to barrier dysfunction is a priority, since sepsis and acute respiratory distress syndrome are still associated with high mortality rates. In the present study, we focus on the effects of the unfolded protein response suppressor (UPR) 4-Phenylbutyrate (4-PBA) in Lipopolysaccharides (LPS)-induced endothelial injury, to investigate the effects of that compound in the corresponding damage. 4-PBA suppressed binding immunoglobulin protein (BiP) - a UPR activation marker - and potentiated LPS - induced signal transducer and activator of transcription 3 (STAT3) and extracellular signal‑regulated protein kinase (ERK) 1/2 activation.

Ceapin-A7 potentiates lipopolysaccharide-induced endothelial injury.

Barrier dysfunction is the hallmark of severe lung injury, including acute respiratory distress syndrome. Efficient medical countermeasures to counteract endothelial hyperpermeability do not exist, hence the mortality rates of disorders related to barrier abnormalities are unacceptable high. The unfolded protein response is a highly conserved mechanism, which aims to support the cells against endoplasmic reticulum stress, and ATF6 is a protein sensor that triggers its activation.

Growth hormone-releasing hormone antagonists counteract hydrogen peroxide - induced paracellular hyperpermeability in endothelial cells.

Growth Hormone-Releasing Hormone (GHRH) is a hypothalamic peptide which regulates the release of Growth Hormone from the anterior pituitary gland, and has been involved in inflammatory processes. On the other hand, GHRH antagonists (GHRHAnt) were developed to counteract those effects. Herein we demonstrate for the first time that GHRHAnt can suppress hydrogen peroxide (HO) - induced paracellular hyperpermeability in bovine pulmonary artery endothelial cells.

Growth hormone-releasing hormone antagonists protect against hydrochloric acid-induced endothelial injury in vitro.

Growth hormone-releasing hormone (GHRH) regulates the synthesis of growth hormone from the anterior pituitary gland, and it is involved in inflammatory responses. On the other hand, GHRH antagonists (GHRHAnt) exhibit the opposite effects, resulting in endothelial barrier enhancement. Exposure to hydrochloric acid (HCL) is associated with acute and chronic lung injury.

Growth Hormone-Releasing Hormone Antagonist JV-1-36 Suppresses Reactive Oxygen Species Generation in A549 Lung Cancer Cells.

Growth hormone-releasing hormone (GHRH) and its receptors are expressed in a variety of human cancers, and have been involved in malignancies. GHRH antagonists (GHRHAnt) were developed to suppress tumor progression and metastasis. Previous studies demonstrate the involvement of reactive oxygen species (ROS) in cancer progression.

Growth Hormone-Releasing Hormone in Endothelial Inflammation.

The discovery of hypothalamic hormones propelled exciting advances in pharmacotherapy and improved life quality worldwide. Growth hormone-releasing hormone (GHRH) is a crucial element in homeostasis maintenance, and regulates the release of growth hormone from the anterior pituitary gland. Accumulating evidence suggests that this neuropeptide can also promote malignancies, as well as inflammation.