Abstract

Objective The goal of this work was to look at the expression and probable role of exosomal long noncoding RNA (lncRNA) GAS5 in gestational diabetes mellitus (GDM), as well as forecast the importance of its interaction with neuropeptides in the progression of the disease. Methods We divided 44 pregnant women visiting the obstetric outpatient clinics at the Affiliated Hospital of Guilin Medical College from January 2021 to December 2021 into healthy and GDM groups. We measured the expression levels of the lncRNA GAS5 in peripheral blood using PCR and compared the expression levels between the 2 groups. The Gene Expression Omnibus (GEO) database and the R software were used to analyse the differences in the genes expressed in the amniotic fluid cells in the GDM and normal groups. catRAPID was used to identify potential target proteins for GAS5. Key neuropeptide-related proteins and potential target proteins of GAS5 were extracted, and protein interaction networks were mapped. AlphaFold 2 was used to predict the structure of the target protein. The ClusPro tool was used to predict protein-protein interactions. ZDOCK was used to further confirm the protein–nucleic acid docking. Results The lncRNA GAS5 was downregulated in the peripheral blood of pregnant women with GDM compared with normal pregnant women. The subcellular localization sites of GAS5 were the nucleus, cytoplasm, and ribosome; in addition, GAS5 was present in exosomes. Intercellular interactions, including neuropeptide receptors, were increased in the amniotic fluid cells of patients with GDM. Venn diagram analysis yielded seven neuropeptide-related proteins and three GAS5 target proteins. Among them, HERC5/TAC1 interacted and GAS5 docked well with HERC5. Conclusion The lncRNA GAS5 in the peripheral blood exosomes in patients with GDM may be a new target for the detection of GDM, and the interaction between GAS5 and HERC5/TAC1 may be involved in the pathogenesis of GDM.

Highlights

  • Gestational diabetes mellitus (GDM) is a common complication that occurs in pregnant women in their middle and late stages of pregnancy and is mainly caused by disorders of glucose metabolism in the body [1]

  • The characteristics of GAS5 expression in the serum of 23 healthy and 21 patients with GDM are shown in Figure 1(a); GAS5 was downregulated in patients with GDM

  • The long noncoding RNA (lncRNA) GAS5 was present in exosomes (Table 1)

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Summary

Introduction

Gestational diabetes mellitus (GDM) is a common complication that occurs in pregnant women in their middle and late stages of pregnancy and is mainly caused by disorders of glucose metabolism in the body [1]. Hypoxia, and obesity are involved in inducing an increase in exosomes during pregnancy, and exosomes may be used as biomarkers for the diagnosis and treatment of gestational diabetes [8, 9]. The results of previous studies indicate that exocrine complex-containing substances can be involved in the mechanistic regulation of maternal pregnancy through multiple pathways. We speculated that exosomes or specific active substances contained within exosomes may be a new form of pathological manifestation of GDM. The composition of active substances present in the plasma exosomes during pregnancy in GDM patients is not completely understood, and further studies are required to understand the relationship between the substances present in exosomes and the pathological manifestations of GDM

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