Maternal serum ADAMTS-9 levels in gestational diabetes: a pilot study

Ülkümen, Burcu Artunç; Uluçay, Safiye; Pala, Halil Gürsoy; Çam, Sırrı

doi:10.1080/14767058.2016.1219717

Cited by 9 publications

(6 citation statements)

References 18 publications

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“…In a previous report, Santiago et al [128], Auburger et al [129], Qu et al [130], Ś et al [131] and Hjortebjerg et al [132] reported that SLC22A5, SH2B3, ITPR3, CALD1 and IGFBP4 expression might be regarded as an indicator of susceptibility to type 1 diabetes mellitus, but these genes might be associated with progression of GDM. Krishnan et al [133], Hu et al [134], Martins et al [135], Prieto-Sánchez et al [136], Sugulle et al [137], Zhao et al [138], Siddiqui et al [139], Han et al [140], Lappas et al [141], Wang et al [142], Artunc-Ulkumen et al [143], Blois et al [144], Vacínová et al [145] and Vilmi-Kerälä et al [146] demonstrated that the expression of CREBRF (CREB3 regulatory factor), STRA6, EGFR (epidermal growth factor receptor), MFSD2A, GDF15, PAK1, VCAM1, IGFBP2, IGFBP7, PRKCA (protein kinase C alpha), ADAMTS9, LGALS1, BIN1, TIMP1 and are associated with progression of GDM. Aquila et al, [147],Chen et al [148], Xie et al [149], Zhang et al [150], Aspit et al [151], Akadam-Teker et al [152], Jiang et al [153], Cetinkaya et al [154], Grond-Ginsbach et al [155], Dong et al [156], Chardon et al [157], Chen et al [158], Yamada et al [159], Hu et al [160], Bobik and Kalinina [161], Schwanekamp et al [162], Liu et al [163], Schroer et al [164], Raza et al [165], Yang et al [166], Azuaje et al [167], Durbin et al [168], Chowdhury et al [169], Wang et al [170], Li et al [171], Lv et al [172], Bertoli-Avella et al [173], Grossman et al [174], Andenæs et al [175] and Chen et al [176] demonstrated that HES1, SPIN1, TBX3, EVA1A, CAP2, BMP1, HSPB8, RDX (radixin), COL5A1, LIMS2, PARVA (parvin alpha), EGFLAM (EGF like, fibronectin type III and laminin G domains), NEXN (nexilin F-actin binding protein), TNFRSF14, TGFBI (transforming growth factor beta induced), HAVCR2, CDH11, COL4A1, COL4A2, COL5A2, SHROOM3, HYAL2, PDLIM3, ETS2, PLSCR4, TGFB3, COL6A2 and LTBP2 could induce cardiovascular diseases, but these genes might be essential for progression of GDM.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus

Vastrad¹,

Vastrad²,

Tengli

2021

Preprint

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Gestational diabetes mellitus (GDM) is one of the metabolic diseases during pregnancy. The identification of the central molecular mechanisms liable for the disease pathogenesis might lead to the advancement of new therapeutic options. The current investigation aimed to identify central differentially expressed genes (DEGs) in GDM. The transcription profiling by array data (E-MTAB-6418) was obtained from the ArrayExpress database. The DEGs between GDM samples and non GDM samples were analyzed with limma package. Gene ontology (GO) and REACTOME enrichment analysis were performed using ToppGene. Then we constructed the protein-protein interaction (PPI) network of DEGs by the Search Tool for the Retrieval of Interacting Genes database (STRING) and module analysis was performed. Subsequently, we constructed the miRNA-hub gene network and TF-hub gene regulatory network by the miRNet database and NetworkAnalyst database. The validation of hub genes was performed through receiver operating characteristic curve (ROC). Finally, the candidate small molecules as potential drugs to treat GDM were predicted by using molecular docking. Through transcription profiling by array data, a total of 869 DEGs were detected including 439 up regulated and 430 down regulated genes. Biological process analysis of GO enrichment analysis showed these DEGs were mainly enriched in reproduction, nuclear outer membrane-endoplasmic reticulum membrane network, identical protein binding, cell adhesion, supramolecular complex and signaling receptor binding. Signaling pathway enrichment analysis indicated that these DEGs played a vital in cell surface interactions at the vascular wall and extracellular matrix organization. Ten genes, HSP90AA1, EGFR, RPS13, RBX1, PAK1, FYN, ABL1, SMAD3, STAT3, and PRKCA in the center of the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network were associated with GDM, according to ROC analysis. Finally, the most significant small molecules were predicted based on molecular docking. Our results indicated that HSP90AA1, EGFR, RPS13, RBX1, PAK1, FYN, ABL1, SMAD3, STAT3, and PRKCA could be the potential novel biomarkers for GDM diagnosis, prognosis and the promising therapeutic targets. The current might be essential to understanding the molecular mechanism of GDM initiation and development.

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Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus

Vastrad¹,

Vastrad²,

Tengli

2021

Preprint

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“…conducted a pilot study evaluating serum levels of ADAMTS9 in patients with GDM. They demonstrated a significant reduction in serum ADAMTS9 levels in GDM patients and proposed that treatments targeting ADAMTS proteins may help to improve diabetes outcomes …”

Section: Discussionmentioning

confidence: 99%

“…They demonstrated a significant reduction in serum ADAMTS9 levels in GDM patients and proposed that treatments targeting ADAMTS proteins may help to improve diabetes outcomes. 13 ADAMTS proteases and proteoglycans are widely expressed in fetal tissues and play an important role in numerous embryological developmental processes, including tissue remodeling, organogenesis, extracellular matrix remodeling and angiogenesis, as well as maternal processes such as cervical dilatation and post-partum uterine involution. 18 Beginning in the early stages of pregnancy, ADAMTS and extracellular matrix proteoglycans expressed in fetal membranes modify the intrauterine microenvironment, leading to insulin resistance in the second and third trimesters of pregnancy.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of second trimester amniotic fluid ADAMTS4, ADAMTS5, interleukin‐6 and tumor necrosis factor‐α levels in patients with gestational diabetes mellitus

Melekoğlu

Çiftçi

Çelik

et al. 2019

J of Obstet and Gynaecol

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Aim To test the hypothesis that altered A Disintegrin and Metalloproteinase Domains with Thrombospondins motifs (ADAMTS) is implicated in the etiopathogenesis of gestational diabetes mellitus (GDM). Methods All pregnant women who underwent elective amniocentesis for karyotype analysis between January 1, 2016, and January 1, 2018, were included in this study. From this cohort, the study group consisting of 20 patients diagnosed with GDM was selected and compared against a control group consisting of 20 age‐ and body mass index (BMI)‐matched patients without GDM. ADAMTS4, ADAMTS5, interleukin‐6 (IL‐6) and tumor necrosis factor alpha (TNF‐α) levels were compared in the second trimester amniotic fluid of patients with GDM and normoglycemic pregnant women. Results No significant differences were observed between GDM and control groups regarding age, BMI, gestational age at amniocentesis and indication for amniocentesis. Mean amniotic fluid ADAMTS4 and ADAMTS5 levels were significantly increased in the GDM group compared with the control group (253.5 ± 18.7 pg/mL and 188.5 ± 21.3 pg/mL, P < 0.001; 192.9 ± 16.4 pg/mL and 154.8 ± 19.9 pg/mL, P = 0.021, respectively). Significant increases in IL‐6 and TNF‐α levels were also detected in the amniotic fluid of GDM patients relative to controls (136.2 ± 17.3 pg/mL and 98.3 ± 11.5 pg/mL, P < 0.001; 154.2 ± 12.5 pg/mL and 86.2 ± 10.8 pg/mL, P < 0.001, respectively). Conclusion The data presented here suggest that increased levels of ADAMTS4, ADAMTS5, IL‐6 and TNF‐α may play an important role in the progression of GDM.

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“…Metalloproteinases serve essential roles in morphogenesis, tissue remodeling, and cell migration, all of which are important in normal or disease processes. From genome-wide association studies (GWAS), Adamts9 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 9) is associated with various human diseases, such as diabetes [1][2][3] , asthma [4] , arthritis [5,6] , artery calci cation [7,8] , macular degeneration [9], and cognitive aging [10] . However, Adamts9-dependent physiological processes, adamts9 expression, and in vivo functions are still poorly understood mainly due to the lack of non-lethal vertebrate knockout animal models.…”

Section: Introductionmentioning

confidence: 99%

Delay in Primordial Germ Cell Migration in Adamts9 Knockout Zebrafish

Carver

Zhu

2021

Preprint

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Adamts9 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 9) is one of few metalloproteinases structurally conserved from C. elegans to humans and is indispensable in germ cell migration in invertebrates. However, adamts9’s roles in germ cell migration in vertebrates has not been examined. In the present study, we found zygotic expression of adamts9 started around germ ring stage and reached peak levels at 3 days post fertilization (dpf) in zebrafish. Germ cell migration completed within 24 hours in wildtype sibling, while a delay in germ cell migration was found at 15 and 24-hours post-fertilization (hpf) in the Adamts9 knockout (KO). However, this delayed effect of Adamts9 KO disappeared at 48 hpf. Our study suggests a conserved function of Adamts9 in germ cell migration among invertebrates and vertebrates. In addition, our results also suggest that Adamts9 is not essential for germ cell migration as reported in C. elegans, possibly due to expansion of Adamts family members and compensatory roles from another metalloproteinase in vertebrates. Further studies are required in order to elucidate the functions and mechanisms of metalloproteinases in germ cell migration and gonad formation in vertebrates.

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Maternal serum ADAMTS-9 levels in gestational diabetes: a pilot study

Abstract: ADAMTS-9 levels were significantly lower in GDM pregnancies. This may help to understand the mechanism of GDM pathogenesis. In future, target treatments with ADAMTS proteins may help to improve the severity of diabetes pathogenesis.

Cited by 9 publications

References 18 publications

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus

Evaluation of second trimester amniotic fluid ADAMTS4, ADAMTS5, interleukin‐6 and tumor necrosis factor‐α levels in patients with gestational diabetes mellitus

Delay in Primordial Germ Cell Migration in Adamts9 Knockout Zebrafish

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