Chen Guoyou, Wang Jinming, Jing Yisi, Li Chunxiang, Zhang Wenyue, Yang Shuang, Song Ye, Wang Xin, Liu Jincheng, Yu Dejun, Xu Zhichun
Daqing Campus, Harbin Medical University, Daqing, China.
Gynecology Department, Dating Oil Field General Hospital, Daqing, China.
Front Pharmacol. 2022 May 5;13:818952. doi: 10.3389/fphar.2022.818952. eCollection 2022.
Nowadays, short stature (SS) in childhood is a common condition encountered by pediatricians, with an increase in not just a few families. Various studies related to the variations in key metabolites and their biological mechanisms that lead to SS have increased our understanding of the pathophysiology of the disease. However, little is known about the role of metabolite variation in different types of childhood SS that influence these biological processes and whether the understanding of the key metabolites from different types of childhood SS would predict the disease progression better. We performed a systematic investigation using the metabonomics method and studied the correlation between the three groups, namely, the control, idiopathic short stature (ISS), and short stature due to growth hormone deficiency (GHD). We observed that three pathways (viz., purine metabolism, sphingolipid signaling pathway, and sphingolipid metabolism) were significantly enriched in childhood SS. Moreover, we reported that two short peptides (Thr Val Leu Thr Ser and Trp Ile Lys) might play a significant role in childhood SS. Various metabolites in different pathways including 9,10-DiHOME, 12-HETE, 12(13)-EpOME, arachidonic acid methyl ester, glycerophospho-N-arachidonoyl ethanolamine, curvulinic acid (2-acetyl-3,5-dihydroxyphenyl acetic acid), nonanoic acid, and N'-(2,4-dimethylphenyl)-N-methylformamidine in human serum were compared between 60 children diagnosed with SS and 30 normal-height children. More investigations in this area may provide insights and enhance the personalized treatment approaches in clinical practice for SS by elucidating pathophysiology mechanisms of experimental verification.
如今,儿童期身材矮小(SS)是儿科医生常见的病症,涉及的家庭数量不止少数有所增加。各种关于导致SS的关键代谢物变化及其生物学机制的研究增进了我们对该疾病病理生理学的理解。然而,关于代谢物变化在影响这些生物学过程的不同类型儿童期SS中的作用,以及从不同类型儿童期SS中对关键代谢物的理解是否能更好地预测疾病进展,我们所知甚少。我们采用代谢组学方法进行了系统研究,并研究了三组之间的相关性,即对照组、特发性身材矮小(ISS)组和生长激素缺乏症(GHD)导致的身材矮小组。我们观察到三条途径(即嘌呤代谢、鞘脂信号通路和鞘脂代谢)在儿童期SS中显著富集。此外,我们报告了两种短肽(苏氨酸-缬氨酸-亮氨酸-苏氨酸-丝氨酸和色氨酸-异亮氨酸-赖氨酸)可能在儿童期SS中发挥重要作用。比较了60名被诊断为SS的儿童和30名正常身高儿童血清中的各种代谢物,这些代谢物存在于不同途径中,包括9,10-二羟基十八碳二烯酸、12-羟基二十碳四烯酸、12(13)-环氧十八碳三烯酸、花生四烯酸甲酯、甘油磷酸-N-花生四烯酰乙醇胺、弯曲菌素酸(2-乙酰基-3,5-二羟基苯基乙酸)、壬酸和N'-(2,4-二甲基苯基)-N-甲基甲脒。该领域的更多研究可能会通过阐明实验验证的病理生理机制,为临床实践中SS的个性化治疗方法提供见解并加以改进。