Up-regulation of TGFBI and TGFB2 in the plasma of gestational diabetes mellitus patients and its clinical significance

Abstract

Background Gestational diabetes mellitus (GDM) reflects a deficiency in the relative need for insulin during pregnancy, as well as temporary metabolic stress in the placenta and fetus. Our study aimed to research the potential diagnostic value of transforming growth factor-beta-induced protein ig-h3 (TGFBI) and transforming growth factor beta-2 proprotein (TGFB2) for GDM patients. Methods Online database Gene Expression Omnibus (GEO) was used to screen for different expressed genes (DEGs) associated with GDM. Meanwhile, KEGG and GO were used to analyze the molecular functions as well as pathways of enriched DEGs. One hundred ten pregnant women diagnosed with GDM and 110 healthy controls were enrolled, of whose placenta and fasting venous blood samples were collected. mRNA expression levels were determined by real-time quantitative polymerase chain reaction (RT-qPCR), and fasting blood glucose (FBG) was measured by the clinical lab of hospital. Furthermore, receiver operating characteristics curve (ROC) analysis was performed to evaluate the sensitivity and specificity of detection indexed in the placenta and plasma of GDM patients. Finally, Pearson and Spearman analysis was used for the correlation analysis. Results After GEO data analysis, TGFBI and TGFB2 were identified as the most significantly up-regulated genes of GDM. TGFBI and TGFB2 expressions in placenta and plasma samples of GDM patients were in line with bioinformatic analysis. Meanwhile, the area under the curve (AUC) of TGFBI in the placenta and plasma for the diagnosis of GDM were 0.8783 (95% CI, 0.8281 to 0.9284) and 0.7832 (95% CI, 0.7215 to 0.8449) while for TGFB2 were 0.9225 (95% CI, 0.8829 to 0.9621) and 0.8961 (95% CI, 0.8526 to 0.9396). Besides, levels of TGFBI along with TGFB2 in the placenta were positively correlated with that in the plasma of GDM patients. Furthermore, both TGFBI and TGFB2 expressions in the plasma were positively correlated with FBG levels of the GDM patients. Conclusions TGFBI and TGFB2 were up-regulated in the placenta and plasma of GDM patients, and TGFBI and TGFB2 in the plasma are potent to be diagnostic markers for the GDM. Keywords Biomarker • Different expressed genes (DEGs) • Gestational diabetes mellitus (GDM) • GEO database • Transforming growth factor beta-2 proprotein (TGFB2) • Transforming growth factor-beta-induced protein ig-h3 (TGFBI)

A Promising Biomarker and Therapeutic Target in Patients with Advanced PDAC: The Stromal Protein βig-h3

“…Our present results need to be confirmed in larger cohort of patient with stage IV PDAC in which the correlation between the [beta]ig-h3 tumor staining and serum level is to be explored, because tumor samples failed to be available for such experiment in this cohort owing to transfer/administrative constraints. It has been reported that in gestastional diabetes there was an increase of tgbi mRNA in the plasma [15]. Therefore, further investigation in correlation with other related physipathological states/diseases should be pursued.. Lastly, results from the ongoing stages I-III BIGHPANC cohorts will be of crucial importance to validate the increase in βig-h3 serum levels from stage I to stage IV.…”

Extracellular matrix‐related and serine protease proteins in the amniotic fluid of women with early preterm labor: Association with spontaneous preterm birth, intra‐amniotic inflammation, and microbial invasion of the amniotic cavity

“…87 Similarly, Zhou et al also found that the expression of TGFBI was upregulated in the placenta and plasma of patients with gestational diabetes, which is a state of low-grade systemic inflammation, 88 compared to that in the corresponding samples obtained from healthy controls. 89 Of note, in the context of PTL induced by uterine overdistention, Adams et al…”

Construction of a novel miRNA regulatory network and identification of target genes in gestational diabetes mellitus by integrated analysis

“…COL4A1 was involved in diabetic tubulointerstitial injury (Zeng et al, 2019) and COL5A2 participated in the progression of uterine fibroids (Giri et al, 2017) and colon adenocarcinoma (Wei et al, 2020), although their functions were not fully understood for GDM development. TGFBI, upregulated in the placenta and the plasma of GDM, was positively associated with FBG levels in GDM patients (Han et al, 2014;Zhou et al, 2021). SLC7A5 enables L-leucine/L-tryptophan transmembrane transporter activity and is a part of amino acid transport complex.…”

“…TGFB2 encodes a secreted ligand of the transforming growth factor-beta (TGF-β) superfamily of proteins, which is involved in the pathogenesis of diabetes and complications. Zhou et al reported that TGFB2 is an upregulated gene in the plasma of GDM patients and correlated with FBG levels in GDM patients ( Zhou et al, 2021 ), which suggested that TGFB2 might play vital roles in the pathogenesis of GDM. FBN2 encodes a peptide hormone placensin, which stimulates cAMP-PKA signaling, glucose secretion and trophoblast invasion in human trophoblastic cells.…”