The effect of gestational diabetes on identification of key genes and pathways in human umbilical vein endothelial cell by integrated bioinformatics analysis

Abstract

Maternal diabetes may lead to long-term risks for the offspring. The study aims at identifying the potential crucial genes and pathways associated with foetal metabolism and malformation of gestational diabetes mellitus (GDM). Gene Expression Series 49524 and 87295 were downloaded from Gene Expression Omnibus database, including eight from GDM and eight from non-GDM. A total of 35 differentially expressed genes were identified. Gene ontology functional annotation and signalling pathway analyses were performed. Four hub genes were identified by protein–protein interaction network: SHH, E2F1, STAT1, and HOXA9. The four hub genes were assessed by western blot and real-time quantitative PCR in clinical samples. The results of this data mining and integration help to reveal the pathophysiologic and molecular mechanism imprinted in primary umbilical cord-derived cells from GDM offspring. These genes and pathways identified are potential stratification biomarkers and provide further insight for developing therapeutic intervention for the offspring of diabetic mothers. Impact statement What is already known on this subject? Maternal diabetes may lead to long-term risks for the offspring. A high glucose environment might change the umbilical cord expression of genes implicated in foetal metabolism and development. However, underlying molecular mechanisms have not been investigated thoroughly. What do the results of this study add? GO functional annotation showed that the biological functions of differentially expressed genes mainly involved in metanephros development, salivary gland morphogenesis, fat cell differentiation, vasculogenesis, muscle cell proliferation, heart morphogenesis and Wnt signalling pathway. Signalling pathway analyses found that these differentially expressed genes mainly implicated in the apoptosis, cell cycle, Hedgehog, P53, and NOTCH signalling pathway. Four hub genes were identified by protein-protein interaction network: SHH, E2F1, STAT1 and HOXA9. What are the implications of these findings for clinical practice and/or further research? The genes and pathways identified in the present study are potential stratification biomarkers and provide further insight for developing therapeutic intervention for the offspring of diabetic mothers.