一种内源性羊水来源的十肽可改善肺发育和高氧损伤。

An endogenous amniotic fluid-derived 10-amino acid peptide improves lung development and hyperoxia injury.

作者信息

Li Baihe, Chen Xu, Ma Weihui, Li Ning, Chen Qin, Liao Jinfeng, Luo Sanfeng, Lu Xiaomei, Zhang Yaozhong, Li Siping, Wang Xingyun, Xu Fengdan

机构信息

Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan, China.

Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Transl Pediatr. 2023 Jan 31;12(1):46-55. doi: 10.21037/tp-22-681. Epub 2023 Jan 16.

DOI:10.21037/tp-22-681

PMID:36798938

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9926127/

Abstract

BACKGROUND

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that occurs in preterm infants and lacks effective treatment. We aim to reveal the relationship between amniotic fluid (AF) peptides and lung development by analyzing the differences in the composition of AF peptides at different gestational periods, thus providing a new means of prevention and treatment for BPD.

METHODS

Based on the stages of lung development, we collected AF by amniocentesis in two different gestational periods, using the 25th week of pregnancy as the cut-off. We conducted a peptide omics analysis of these AF samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Additionally, we verified the regulatory effects of hyperoxia and the peptide COL5A2 on BPD-related cells [(mouse lung epithelial (MLE-12) cells] by 5-Ethynyl-2'-deoxyuridine (EdU) staining, JC-1 staining, flow cytometry, and reactive oxygen species (ROS) assay.

RESULTS

There were 131 differentially expressed peptides, including 85 up-regulated and 46 down-regulated [fold change (FC) ≥1.2 or ≤1/1.2, P0.05], in the ≥25 weeks' gestation group compared to the <25 weeks' gestation group. Further bioinformatics analysis revealed that the precursor proteins of the differentially expressed peptides between these two groups were involved in the regulation of the developmental process, anatomical structure development, and other biological processes, suggesting that these differential peptides may play a key role in lung development. We found peptide COL5A2 with the sequence GPPGEPGPPG and verified the regulatory effects of COL5A2 on the proliferation, apoptosis, cell viability, and ROS levels of MLE-12 cells by cell assays.

CONCLUSIONS

In this study, peptidomic studies using AF from different gestational periods revealed that peptides in AF may be involved in lung development. They could be used in the future to assist in the postnatal development of preterm infants and provide new therapeutic prospects for BPD.

摘要

背景

支气管肺发育不良（BPD）是一种发生于早产儿的慢性肺部疾病，且缺乏有效的治疗方法。我们旨在通过分析不同孕周羊水（AF）肽组成的差异，揭示AF肽与肺发育之间的关系，从而为BPD提供新的防治手段。

方法

根据肺发育阶段，我们在两个不同孕周通过羊膜腔穿刺收集AF，以妊娠第25周作为分界点。我们使用液相色谱-串联质谱（LC-MS/MS）分析对这些AF样本进行肽组学分析。此外，我们通过5-乙炔基-2'-脱氧尿苷（EdU）染色、JC-1染色、流式细胞术和活性氧（ROS）检测，验证了高氧和肽COL5A2对BPD相关细胞[小鼠肺上皮（MLE-12）细胞]的调节作用。

结果

与妊娠<25周组相比，妊娠≥25周组有131种差异表达肽，其中85种上调，46种下调[倍数变化（FC）≥1.2或≤1/1.2，P<0.05]。进一步的生物信息学分析表明，这两组之间差异表达肽的前体蛋白参与了发育过程、解剖结构发育和其他生物学过程的调节，提示这些差异肽可能在肺发育中起关键作用。我们发现了序列为GPPGEPGPPG的肽COL5A2，并通过细胞实验验证了COL5A2对MLE-12细胞增殖、凋亡、细胞活力和ROS水平的调节作用。