Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Sci Rep. 2019 May 2;9(1):6815. doi: 10.1038/s41598-019-43321-4.
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.
六肽 WKYMVm 是一种强形式的趋化因子受体（FPR）2 激动剂，具有促血管生成、抗炎和抗细胞凋亡作用。然而，其在支气管肺发育不良（BPD）中的治疗效果尚未得到验证。在这里，我们研究了 WKYMVm 是否通过上调 FPR2 来减轻高氧诱导的肺炎症和随后的损伤。在体外评估了人脐静脉内皮细胞（HUVEC）的增殖和管形成能力，以及细胞外信号调节激酶（ERK）磷酸化水平。新生小鼠从出生开始连续 14 天暴露于 80%氧气或室内空气。WKYMVm（2.5mg/kg）从出生后第 5 天至第 8 天每天腹腔内给药。在 P14 时，处死小鼠进行组织病理学和形态计量学分析。随着 FPR2 和 p-ERK 的上调，WKYMVm 促进了 HUVEC 细胞的增殖和管形成。此外，WKYMVm 促进了人肺微血管内皮细胞（HULEC-5a）和鼠肺内皮和上皮细胞的体外增殖。WKYMVm 显著减轻了高氧诱导的肺炎症，表现为炎症细胞因子、中性粒细胞和肺泡巨噬细胞增加，以及肺泡化和血管生成受损、凋亡细胞数量增加以及体内生长因子水平降低，如血管内皮生长因子和肝细胞生长因子。WKYMVm 通过上调 FPR2 和 p-ERK 减轻高氧诱导的肺损伤和肺炎症。
