Downregulation of hsa_circ_005243 induces trophoblast cell dysfunction and inflammation via the β-catenin and NF-κB pathways in gestational diabetes mellitus

2020 ◽  
Author(s):  
Huiyan Wang ◽  
Wenbo Zhou ◽  
Guangtong She ◽  
Bin Yu ◽  
Lizhou Sun
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Inflammatory Factors ◽  
Cell Proliferation And Migration ◽  
Tnf Α ◽  
And Migration ◽  
In Pregnancy ◽  
Proliferation And Migration

Abstract Background: Gestational diabetes mellitus (GDM) is a common complication in pregnancy that poses a serious threat to the health of both mother and child. While the specific etiology and pathogenesis of this disease are not fully understood, it is thought to arise due to a combination of insulin resistance, inflammation, and genetic factors. Circular RNAs (circRNAs) are a special kind of non-coding RNA that have attracted significant attention in recent years due to their diverse activities, including a potential regulatory role in pregnancy-related diseases, such as GDM. Methods: We previously reported the existence of a novel a circRNA, hsa_circ_005243, which was identified by RNA sequencing. In this study, we examined its expression in 20 pregnant women with GDM and 20 normal controls using quantitative reverse transcription PCR analysis. Subsequent in vitro experiments were conducted following hsa_circ_005243 knockdown in HTR-8/SVneo cells to examine the role of hsa_circ_005243 in cell proliferation and migration, as well as the secretion of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Finally, we examined the expression of β-catenin and nuclear factor kappa-B (NF-κB) signaling pathways to assess their role in GDM pathogenesis.Results: Expression of hsa_circ_005243 was significantly reduced in both the placenta and plasma of GDM patients. Knockdown of hsa_circ_005243 in trophoblast cells significantly suppressed cell proliferation and migration ability. In addition, increased secretion of inflammatory factors (TNF-α and IL-6) was observed after hsa_circ_005243 depletion. Further analyses showed that knockdown of hsa_circ_005243 reduced the expression of β-catenin and increased nuclear NF-κB p65 nuclear translocation. Conclusions: Downregulation of hsa_circ_005243 may be associated with the pathogenesis of GDM via the regulation of β-catenin and NF-κB signal pathways, suggesting a new potential therapeutic target for GDM.

scholarly journals Downregulated hsa_circ_005243 induced trophoblast cell dysfunction and inflammation via β-catenin and NF-κB pathways in gestational diabetes mellitus

2020 ◽  
Author(s):  
Huiyan Wang ◽  
Wenbo Zhou ◽  
Guangtong She ◽  
Bin Yu ◽  
Lizhou Sun
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Gestational Diabetes ◽  
Pregnant Women ◽  
Inflammatory Factors ◽  
Migration Ability ◽  
Cell Proliferation And Migration ◽  
Tnf Α ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Gestational diabetes mellitus(GDM) is a common obstetric pregnancy complication, which poses a serious threat to the health of pregnant women and newborns. The specific etiology and pathogenesis of this disease have not been fully clarified, it is reported to be related with insulin resistance, inflammatory response and genetic factors etc. Circular RNA(circRNA) is a special kind of non-coding RNA, which have been attracted much attention in recent years. It has been reported that circRNAs may play a regulatory role in pregnancy-related diseases, including GDM. Methods: Previously we reported a circRNA, hsa_circ_005243, which was identified by RNA-sequencing. In this study we detected its expression in 20 GDM pregnant women and 20 normal controls using quantitative reverse transcription polymerase chain reaction analysis. Further in vitro experiments were conducted after hsa_circ_005243 knockdown in HTR8-S/Vneo cells, cell proliferation and migration ability was tested, the secretion of inflammatory factors (TNF-α and IL-6) were detected by ELISA. Then we detected the expression of β-catenin and increased nuclear factor kappa-B (NF-κB) signaling pathways which was related to GDM in the mechanism study. Results: We found the expression of hsa_circ_005243 was significantly reduced both in the placenta and plasma of GDM pregnant women. Knockdown of hsa_circ_005243 in trophoblast cells significantly suppressed cell proliferation and migration ability. In addition, increased secretion of inflammatory factors (TNF-α and IL-6) were observed after hsa_circ_005243 depletion. Further mechanism experiments showed that knockdown of hsa_circ_005243 reduced the expression of β-catenin and increased nuclear NF-κB p65 nuclear translocation. Conclusions: Collectively, our study showed that down-regulation of hsa_circ_005243 might be associated with the pathogenesis of GDM through regulating β-catenin and NF-κB signal pathways and suggest a new potential therapeutic target for GDM.

scholarly journals Downregulation of hsa_circ_0005243 induces trophoblast cell dysfunction and inflammation via the β-catenin and NF-κB pathways

2020 ◽  
Author(s):  
Huiyan Wang ◽  
Wenbo Zhou ◽  
Guangtong She ◽  
Bin Yu ◽  
Lizhou Sun
Keyword(s):  
Cell Proliferation ◽  
Nuclear Translocation ◽  
Inflammatory Factors ◽  
Pcr Analysis ◽  
Signal Pathways ◽  
Cell Proliferation And Migration ◽  
Tnf Α ◽  
And Migration ◽  
In Pregnancy ◽  
Proliferation And Migration

Abstract Background: Gestational diabetes mellitus (GDM) is a common complication in pregnancy that poses a serious threat to the health of both mother and child. While the specific etiology and pathogenesis of this disease are not fully understood, it is thought to arise due to a combination of insulin resistance, inflammation, and genetic factors. Circular RNAs (circRNAs) are a special kind of non-coding RNA that have attracted significant attention in recent years due to their diverse activities, including a potential regulatory role in pregnancy-related diseases, such as GDM. Methods: We previously reported the existence of a novel circRNA, hsa_circ_0005243, which was identified by RNA sequencing. In this study, we examined its expression in 20 pregnant women with GDM and 20 normal pregnant controls using quantitative reverse transcription PCR analysis. Subsequent in vitro experiments were conducted following hsa_circ_0005243 knockdown in HTR-8/SVneo cells to examine the role of hsa_circ_0005243 in cell proliferation and migration, as well as the secretion of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Finally, we examined the expression of β-catenin and nuclear factor kappa-B (NF-κB) signaling pathways to assess their role in GDM pathogenesis Results: Expression of hsa_circ_0005243 was significantly reduced in both the placenta and plasma of GDM patients. Knockdown of hsa_circ_0005243 in trophoblast cells significantly suppressed cell proliferation and migration ability. In addition, increased secretion of inflammatory factors (TNF-α and IL-6) was observed after hsa_circ_0005243 depletion. Further analyses showed that knockdown of hsa_circ_0005243 reduced the expression of β-catenin and increased nuclear NF-κB p65 nuclear translocation. Conclusions: Downregulation of hsa_circ_0005243 may be associated with the pathogenesis of GDM via the regulation of β-catenin and NF-κB signal pathways, suggesting a new potential therapeutic target for GDM.

scholarly journals Alteration of serum neuregulin 4 and neuregulin 1 in gestational diabetes mellitus

2021 ◽  
Vol 12 ◽  
pp. 204201882110496
Author(s):  
Lei Zhang ◽  
Bi Lu ◽  
Wenhua Wang ◽  
Shifeng Miao ◽  
Shuru Zhou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fasting Glucose ◽  
Effective Means ◽  
Density Lipoprotein ◽  
Inflammatory Factors ◽  
Neuregulin 1 ◽  
Tnf Α ◽  
Neuregulin 4

Context: Neuregulin 4 (Nrg4) and neuregulin 1 (Nrg1) have been shown to play vital roles in several disorders of glucose metabolism. The pathophysiological role of Nrg4 and Nrg1 in gestational diabetes mellitus (GDM), however, remains poorly understood. We assessed the clinical relevance of the two cytokines in patients with GDM. Methods: The study recruited 36 GDM patients and 38 age-matched, gestational age (24–28 weeks of gestation)–matched, and BMI (during pregnancy)–matched controls in this study. Serum Nrg4 and Nrg1 were measured using ELISA. Inflammatory factors such as IL-6, IL-1β, leptin, TNF-α, and monocyte chemotactic protein 1 (MCP-1) were determined via Luminex technique. Results: Serum Nrg4 in GDM patients was significantly lower than that in the controls, while Nrg1 was significantly higher in the GDM group ( p < 0.01). Inflammatory factors such as IL-6, leptin, and TNF-α were significantly increased in GDM patients, while MCP-1 and IL-1β were not significantly different between the two groups. In addition, serum Nrg4 was negatively correlated with fasting glucose ( r = −0.438, p = 0.008), HOMA-IR ( r = −0.364, p = 0.029), IL-6 ( r = −0.384, p = 0.021), leptin ( r = −0.393, p = 0.018), TNF-α ( r = −0.346, p = 0.039), and MCP-1 ( r = −0.342, p = 0.041), and positively correlated with high-density lipoprotein cholesterol (HDL-C) ( r = −0.357, p = 0.033) in GDM group. Serum Nrg1 was positively correlated with BMI ( r = 0.452, p = 0.006), fasting glucose ( r = 0.424, p = 0.010), HOMA-IR ( r = 0.369, p = 0.027), and triglyceride ( r = 0.439, p = 0.007). The decrease of Nrg4 and the increase of Nrg1 were significantly related to the increased prevalence of GDM. Finally, ROC curve results indicated that Nrg1 combined with IL-6 and TNF-α might be an effective means for GDM screening. Conclusions: Lower circulating Nrg4 and higher circulating Nrg1 serve risk factors of GDM. Nrg1 combined with IL-6 and TNF-α might be a potential tool for GDM screening.

scholarly journals Expression and possible role of Smad3 in postnecrotizing enterocolitis stricture

2022 ◽  
Vol 5 (1) ◽  
pp. e000289
Author(s):  
Rui Chen ◽  
Chengjie Lv ◽  
Xiaoxia Zhao ◽  
Dong Ma ◽  
Dengming Lai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Expression ◽  
Cell Proliferation And Migration ◽  
Tnf Α ◽  
Protein Expressions ◽  
Smad3 Protein ◽  
And Migration ◽  
Emt Markers ◽  
Tgf Β1 ◽  
Proliferation And Migration

ObjectiveTo investigate the expression of Smad3 (mothers against decapentaplegic homolog 3) protein in postnecrotizing enterocolitis stricture and its possible mechanism of action.MethodsWe used immunohistochemistry to detect the expression characteristics of Smad3 and nuclear factor kappa B (NF-κB) proteins in human postnecrotizing enterocolitis stricture. We cultured IEC-6 (crypt epithelial cells of rat small intestine) in vitro and inhibited the expression of Smad3 using siRNA technique. Quantitative PCR, western blotting, and ELISA were used to detect the changes in transforming growth factor-β1 (TGF-β1), NF-κB, tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and zonula occludens-1 (ZO-1) messenger RNA (mRNA) and protein expressions in IEC-6 cells. CCK8 kit and Transwell cellular migration were used to detect cell proliferation and migration. Changes in epithelial–mesenchymal transition (EMT) markers (E-cadherin and vimentin) in IEC-6 cells were detected by immunofluorescence technique.ResultsThe results showed that Smad3 protein and NF-κB protein were overexpressed in narrow intestinal tissues and that Smad3 protein expression was positively correlated with NF-κB protein expression. After inhibiting the expression of Smad3 in IEC-6 cells, the mRNA expressions of NF-κB, TGF-β1, ZO-1, and VEGF decreased, whereas the mRNA expression of TNF-α did not significantly change. TGF-β1, NF-κB, and TNF-α protein expressions in IEC-6 cells decreased, whereas ZO-1 and intracellular VEGF protein expressions increased. IEC-6 cell proliferation and migration capacity decreased. There was no significant change in protein expression levels of EMT markers E-cadherin and vimentin and also extracellular VEGF protein expression.ConclusionsWe suspect that the high expression of Smad3 protein in postnecrotizing enterocolitis stricture may promote the occurrence and development of secondary intestinal stenosis. The mechanism may be related to the regulation of TGF-β1, NF-κB, TNF-α, ZO-1, and VEGF mRNA and protein expression. This may also be related to the ability of Smad3 to promote epithelial cell proliferation and migration.

scholarly journals IL-1β Impaired Diabetic Wound Healing by Regulating MMP-2 and MMP-9 through the p38 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jiezhi Dai ◽  
Junjie Shen ◽  
Yimin Chai ◽  
Hua Chen
Keyword(s):  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Human Fibroblasts ◽  
Diabetic Patients ◽  
Diabetic Wound ◽  
Fibroblast Migration ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Diabetes mellitus is one of the most prominent metabolic disorders in the world, and insulin resistance in diabetic patients leads to several complications including increased inflammation and delayed wound healing. Fibroblast migration and reepithelialization play a significant role in wound healing. In this study, we explored the effects of IL-1β signaling on proliferation and migration of human fibroblasts from diabetic wound tissues. We observed elevated levels of IL-1β in samples from diabetic patients when compared to normal wound tissues. At high concentrations, IL-1β inhibited cell proliferation and migration in ex vivo fibroblast cultures. Moreover, expression of matrix metalloproteinases (MMPs) was upregulated, and tissue inhibitor of metalloproteinases (TIMPs) was downregulated in diabetic wound tissues and cells. These effects were regulated by levels of IL-1β. Furthermore, IL-1β induced p38 phosphorylation thereby activating the p38 MAPK pathway that in turn regulated the expression of MMPs and TIMPs. Together, our study identifies a novel mechanism behind delayed wound closure in diabetes mellitus that involves IL-1β-dependent regulation of cell proliferation and migration.

Nelumbo nucifera leaf polyphenol extract and gallic acid inhibit TNF-α-induced vascular smooth muscle cell proliferation and migration involving the regulation of miR-21, miR-143 and miR-145

2020 ◽  
Vol 11 (10) ◽  
pp. 8602-8611
Author(s):  
Dai-Jung Chung ◽  
Yi-Liang Wu ◽  
Mon-Yuan Yang ◽  
Kuei-Chuan Chan ◽  
Huei-Jane Lee ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Gallic Acid ◽  
Cell Proliferation And Migration ◽  
Tnf Α ◽  
Rho Family ◽  
And Migration ◽  
Kinase Pathway ◽  
Proliferation And Migration

The NLPE and GA potentially prevent atherosclerosis by inhibiting VSMC migration and proliferation. The mechanisms involve the regulation of the miRNA in PTEN, Ras/extracellularsignal-regulated kinase pathway, and Rho family proteins.

IGFs and IGF-Binding Proteins in Pregnancy and Gestational Diabetes Mellitus

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1412-P
Author(s):  
KATEřINA ANDERLOVÁ ◽  
PATRIK SIMJAK ◽  
ANNA CINKAJZLOVA ◽  
JANA KLOUCKOVA ◽  
HELENA KRATOCHVILOVA ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Binding Proteins ◽  
Igf Binding Proteins ◽  
Igf Binding ◽  
In Pregnancy
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