WKYMVm hexapeptide, a strong formyl peptide receptor 2 agonist, attenuates hyperoxia-induced lung injuries in newborn mice.

Abstract

The hexapeptide WKYMVm, which is a strong formyl peptide receptor (FPR) 2 agonist, exhibits pro-angiogenic, anti-inflammatory and anti-apoptotic properties. However, its therapeutic efficacy in bronchopulmonary dysplasia (BPD) has not been tested to date. Here, we investigated whether WKYMVm attenuates hyperoxia-induced lung inflammation and ensuing injuries by upregulating FPR2. The proliferation and tube formation ability of human umbilical vein endothelial cells (HUVECs), along with the level of extracellular signal regulated kinase (ERK) phosphorylation, were evaluated in vitro. Newborn mice were randomly exposed to 80% oxygen or room air for 14 days starting at birth. WKYMVm (2.5 mg/kg) was intraperitoneally administrated daily from postnatal day (P) 5 to P8. At P14, mice were sacrificed for histopathological and morphometric analyses. Along with upregulation of FPR2 and p-ERK, WKYMVm promoted HUVEC cell proliferation and tube formation in vitro. Additionally, WKYMVm promoted proliferation of human pulmonary microvascular endothelial cells (HULEC-5a) and murine pulmonary endothelial and epithelial cells in vitro. WKYMVm significantly attenuated hyperoxia-induced lung inflammation, as evidenced by increased inflammatory cytokines, neutrophils, and alveolar macrophages, and resultant lung injuries, which included impaired alveolarization and angiogenesis, an increased number of apoptotic cells, and reduced levels of growth factors in vivo, such as vascular endothelial growth factor and hepatocyte growth factor. WKYMVm attenuates hyperoxia-induced lung injuries and lung inflammation by upregulating FPR2 and p-ERK.

• Authors: Young Eun Kim, Won Soon Park, So Yoon Ahn, Dong Kyung Sung, Se In Sung, Jae Ho Kim, Yun Sil Chang
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 6815 (05 02 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 31048743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inducing Agents
• Biomarkers
• Cytokines
• Inflammation Mediators
• Oligopeptides
• Receptors, Formyl Peptide
• Trp-Lys-Tyr-Met-Val-Met
• formyl peptide receptor 2, mouse
• Extracellular Signal-Regulated MAP Kinases

Topics

• Angiogenesis Inducing Agents (pharmacology)
• Animals
• Animals, Newborn
• Biomarkers
• Biopsy
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cytokines (metabolism)
• Disease Models, Animal
• Endothelial Cells (drug effects, metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gene Expression
• Hyperoxia (metabolism)
• Immunohistochemistry
• Inflammation Mediators
• Lung Injury (diagnosis, drug therapy, etiology, metabolism)
• Mice
• Oligopeptides (pharmacology)
• Phosphorylation
• Rats
• Receptors, Formyl Peptide (antagonists & inhibitors)
• Respiratory Mucosa (immunology, metabolism)