维生素D与胰岛素样生长因子1在儿童体格发育中的相关性研究

Correlation between vitamin D and IGF1 in childrens physical development

关键词:  维生素D  胰岛素样生长因子1  体格发育

Key words:  vitamin D  insulin-like growth factor 1  physical development

摘要:

目的探讨维生素D与IGF1在儿童体格发育中的相关性及二者相互作用的机制。 方法收集3~15岁生长发育期儿童的一般信息及实验室检查结果，分析维生素D与胰岛素样生长因子1(insulin-like growth factor 1, IGF1)的相关性。同时对维生素D缺乏儿童予维生素D 2 000 IU/d口服治疗3个月，随访血清维生素D、IGF1水平。最后对身材矮小且存在维生素D不足/缺乏儿童与身高及维生素D水平正常儿童进行mRNA测序，检测其维生素D受体(vitamin D receptor, VDR)、IGF1、胰岛素样生长因子受体(insulin-like growth factor 1, IGF1R)基因表达差异，筛选差异基因，进行信号通路、基因本体富集分析。 结果维生素D缺乏儿童较正常儿童存在矮小身材比例更高，相关性分析结果提示IGF1与维生素D存在正相关性。维生素D缺乏儿童经补充维生素D治疗后，其血清维生素D及IGF1水平较前有显著升高。维生素D缺乏儿童与正常儿童相比，VDR基因表达无差异，IGF1、IGF1R基因表达明显减低。GO富集分析结果提示维生素D参与G蛋白偶联和蛋白质磷酸化过程，KEGG富集分析结果提示维生素D参与MAPK蛋白质磷酸化级联反应通路，G蛋白家族信号通路，生长激素的合成、分泌和作用信号通路，IGF1、转化生长因子-β(transforming growth factor-β, TGF-β)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)和核因子κB(nuclear factor κ-B, NF-κB)等骨骼的形成与稳定相关通路，破骨细胞分化等调控骨骼细胞活动通路。 结论维生素D参与儿童骨骼生长，影响儿童体格发育。IGF1与维生素D呈正相关，补充维生素D可以促进维生素D和IGF1水平提高，可能是维生素D的基因组代谢途径直接促进IGF1、IGF1R基因表达，非基因组途径参与GH的合成分泌和作用间接促进IGF1的产生，或通过MAPK蛋白质磷酸化级联反应调控IGF1R表达。

Abstract:

ObjectiveTo explore the correlation between Vitamin D and insulin-like growth factor 1(IGF1) in childrens physical development and the mechanism of interaction between the two. MethodsThe data of children aged 3-15 years were collected, and the correlation between Vitamin D and IGF1 was analyzed by RStudio V1.4 software. Children with Vitamin D deficiency were treated with Vitamin D 2 000 IU/d orally for 3 months, and the serum vitamin D and IGF1 levels were followed-up. mRNA-sequencing was performed between Vitamin D deficient and normal children to detect the differences in VDR, IGF1, and IGF1R gene expression, differential genes were screened, and signaling pathway and Gene Ontology(GO) analysis were performed too. ResultsChildren with Vitamin D deficiency have a higher rate of short stature than children with normal Vitamin D. The results of correlation analysis showed that there was a positive correlation between IGF1 and Vitamin D. After vitamin D supplementation treatment, the serum Vitamin D and IGF1 levels elevated significantly in children with Vitamin D deficiency. Compared with children with normal Vitamin D, the expression of IGF1 and IGF1R genes was significantly reduced in children with Vitamin D deficiency, but there was no difference in VDR gene expression between the two groups. GO enrichment analysis suggested that vitamin D was involved in G protein coupling and protein phosphorylation processes. KEGG enrichment results suggested that vitamin D was involved in MAPK protein phosphorylation cascade pathway, G protein family signaling pathway, growth hormone synthesis, secretion and action signaling pathway, bone formation and stabilization related pathways such as IGF1, transforming growth factor-β(TGF-β), mammalian target of rapamycin(mTOR) and nuclear factor(NF)-κB, and osteoclast differentiation regulated bone cell activity pathways. ConclusionVitamin D is involved in bone growth and physical development in children. IGF1 is positively correlated with vitamin D. Vitamin D supplementation can promote the increase of vitamin D and IGF1 levels, and the metabolic pathway of vitamin D may directly enhance the expression of IGF1 and IGF1R gene; non-genomic pathway participates in the synthesis, secretion and action of GH indirectly promotes the production of IGF1, or regulates IGF1R expression through MAPK protein phosphorylation cascade.