scholarly journals MiR-6869-5p Induces M2 Polarization by Regulating PTPRO in Gestational Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Pingping Wang ◽  
Zhenzhi Ma ◽  
Zengyan Wang ◽  
Ximei Wang ◽  
Guifeng Zhao ◽  
...  

The role of microRNA (miRNA) in gestational diabetes mellitus has been widely investigated during the last decade. However, the altering effect of miR-6869-5p on immunity and placental microenvironment in gestational diabetes mellitus is largely unknown. In our study, the expression of miR-6869-5p was documented to be significantly decreased in placenta-derived mononuclear macrophages, which was also negatively related to PTPRO. Besides, PTPRO was negatively regulated by miR-6869-5p in placenta-derived mononuclear macrophages. In vitro, miR-6869-5p inhibited macrophage proliferation demonstrated by EdU and CCK-8 experiments. The inflammatory response in macrophages was also significantly inhibited by miR-6869-5p, which could regulate PTPRO as a target documented by luciferase reporter assay. Moreover, miR-6869-5p promoted M2 macrophage polarization and thus restrain inflammation. Accordingly, miR-6869-5p is involved in maintaining placental microenvironment balance by preventing from inflammation and inducing M2 macrophages in gestational diabetes mellitus.

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Pingping Wang ◽  
Zengfang Wang ◽  
Guojie Liu ◽  
Chengwen Jin ◽  
Quan Zhang ◽  
...  

MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ashley Toney ◽  
Soonkyu Chung

Abstract Objectives Macrophage polarization into pro-inflammatory M1 status is associated with the pathologic progression of adipose remodeling, while M2 polarization is linked with the resolution of inflammation. Urolithin A (UroA) is a gut metabolite derived from ellagic acid found in berries and nuts. Emerging evidence suggests UroA exerts anti-inflammatory function, but the underlying mechanism remains unknown. This study aims to test the hypothesis that UroA attenuates adipose inflammation by promoting M2 macrophage polarization. Methods To investigate the direct role of UroA in vitro, primary bone marrow-derived macrophages (BMDM) were stimulated with LPS for M1 polarization or IL-4/IL-13 for M2 polarization. Oxygen consumption rate was determined in BMDM by Seahorse extracellular flux analyzer. The anti-inflammatory role of UroA is validated by pro-IL-1β Gaussia luciferase (iGLuc) reporter assay and IL-1β secretion in J774 macrophages. Additionally, C57BL/6 mice were fed with a HF diet for 12 weeks along with UroA administration. The M1/M2 polarization status were examined in adipose tissue macrophages (ATM) and peritoneal macrophages by qPCR and protein markers. Results UroA treatment in BMDM in vitro significantly decreased Il-1β (P < 0.001), while increasing M2 markers of Arg1, Ch313 and Mgl2 (P < 0.01). UroA treatment suppressed NLRP3 inflammasome activation in J774 macrophages by decreasing iGLuc activity and IL-1β secretion in a dose-dependent manner. In vivo, UroA administration reduced HF-induced adipocyte hypertrophy, inflammatory markers, and ATM recruitment (P < 0.01) in the adipose tissue. Consistently, UroA suppressed M1 polarization but switched to M2 polarization in peritoneal macrophages, evidenced by decreased M1 signature genes of Cd11c, Tnf-α, Il-6, and Il-1β (P < 0.01), while elevated M2 markers of Ch313 and Mgl2 (P < 0.05). Lastly, UroA not only inhibits HF-driven pathogenic remodeling of adipose tissue, but also promote mitochondrial function and biogenesis. Conclusions UroA attenuates HF-driven pathologic remodeling of adipose tissue by favoring M2 macrophage polarization and augmenting mitochondrial function. Intake of UroA-producing foods may be a promising intervention strategy to mitigate obesity-mediated chronic inflammation and metabolic dysfunction. Funding Sources United States Department of Agriculture National Institute for Food and Agriculture.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wei Liu ◽  
Muyu Yu ◽  
Feng Chen ◽  
Longqing Wang ◽  
Cheng Ye ◽  
...  

Abstract Background Many patients suffer from implant loosening after the implantation of titanium alloy caused by immune response to the foreign bodies and this could inhibit the following osteogenesis, which could possibly give rise to aseptic loosening and poor osteointegration while there is currently no appropriate solution in clinical practice. Exosome (Exo) carrying miRNA has been proven to be a suitable nanocarrier for solving this problem. In this study, we explored whether exosomes overexpressing miR-181b (Exo-181b) could exert beneficial effect on promoting M2 macrophage polarization, thus inhibiting inflammation as well as promoting osteogenesis and elaborated the underlying mechanism in vitro. Furthermore, we aimed to find whether Exo-181b could enhance osteointegration. Results In vitro, we firstly verified that Exo-181b significantly enhanced M2 polarization and inhibited inflammation by suppressing PRKCD and activating p-AKT. Then, in vivo, we verified that Exo-181b enhanced M2 polarization, reduced the inflammatory response and enhanced osteointegration. Also, we verified that the enhanced M2 polarization could indirectly promote the migration and osteogenic differentiation by secreting VEGF and BMP-2 in vitro. Conclusions Exo-181b could suppress inflammatory response by promoting M2 polarization via activating PRKCD/AKT signaling pathway, which further promoting osteogenesis in vitro and promote osteointegration in vivo. Graphic abstract


Author(s):  
Bin Qi ◽  
Cheng Yang ◽  
Zhanpeng Zhu ◽  
Hao Chen

Glioma is a primary intracranial tumor with high incidence and mortality. The oncogenic role of EZH2 has been reported in glioma. EZH2 inhibited microRNA-454-3p (miR-454-3p) by binding to its promoter in chondrosarcoma cells. Therefore, our study aimed to identify whether EZH2 regulated M2 macrophage polarization in glioma via miR-454-3p. Clinical samples of different grades of glioma and glioma cells were collected and immunohistochemistry and RT-qPCR demonstrated that EZH2 was highly expressed in glioma tissues. Expression of EZH2 was positively correlated with the degree of M2 macrophage polarization in glioma tissues. EZH2 was silenced by lentivirus in glioma cells, which were subsequently co-cultured with macrophages to evaluate its effect on macrophage polarization. miR-454-3p, a down-regulated miR in glioma, was found to be increased after silencing of EZH2. Furthermore, MethPrimer analysis showed that EZH2 silencing inhibited the DNA methylation level of miR-454-3p. Additionally, MS-PCR, dual-luciferase reporter, RIP and RNA pull down assays revealed that miR-454-3p promoted PTEN expression by inhibiting m6A modification through binding to the enzyme YTHDF2. Either inhibition of miR-454-3p or PTEN resulted in promotion of M2 macrophage polarization. Collectively, histone methyltransferase EZH2 inhibited miR-454-3p through methylation modification and promoted m6A modification of PTEN to induce glioma M2 macrophage polarization.


2021 ◽  
Author(s):  
Li Liu ◽  
Haiying Wu# ◽  
Xianghong Cheng

Abstract Objective: Gestational diabetes mellitus (GDM) is often accompanied by cardiovascular injury (CI), while the specific pathology remains largely unknown. The purpose of this study was to investigate the role of Polynucleotide Phosphorylase (PNPase) in GDM-CI.Methods: GDM-CI rats were modeled by giving high-glucose and high-saturated fat compound feed, and PNPase and miR-26a expression in rats was determined. Vascular smooth muscle cells (VSMCs) were isolated, and cells were transfected with si-PNPase, miR-26a mimic, or si-PNPase + miR-26a inhibitor. Cell proliferation, apoptosis and migration of VSMCs were measured by CCK-8 assay, flow cytometry, and scratch test. Dual-luciferase reporter gene assay was performed to verify the targeting relationship between miR-26a and PTEN. RT-qPCR was implemented to detect the expression levels of miR-26a and PTEN among cells in each group.Results: GDM-CI increased PNPase expression and decreased miR-26a expression in cardiovascular tissues of GDM-CI rats. Silencing PNPase and miR-26a upregulation reduced VSMC apoptosis, and enhanced proliferation and migration abilities in GDM-CI. Treatment with miR-26a inhibitor reversed the alleviating effect of inhibiting PNPase expression on GDM-CI. There was a targeting relationship between miR-26a and PTEN, and miR-26a mimic inhibited the expression of PTEN. Suppressed PTEN was found to relieve the GDM-CI.Conclusion: This study suggests that suppression of PNPase alleviates GDM-CI through up-regulating miR-26a and down-regulating PTEN.


2019 ◽  
Vol 25 (22) ◽  
pp. 2467-2473 ◽  
Author(s):  
Enrique Reyes-Muñoz ◽  
Federica Di Guardo ◽  
Michal Ciebiera ◽  
Ilker Kahramanoglu ◽  
Thozhukat Sathyapalan ◽  
...  

Background: Gestational Diabetes Mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, represents one of the most common maternal-fetal complications during pregnancy and it is associated with poor perinatal outcomes. To date, GDM is a rising condition over the last decades coinciding with the ongoing epidemic of obesity and Type 2 Diabetes Mellitus (T2DM). Objective: The aim of this review is to discuss the role of diet and nutritional interventions in preventing GDM with the explanation of the special role of myo-inositol (MI) in this matter. Methods: We performed an overview of the most recent literature data on the subject with particular attention to the effectiveness of diet and nutritional interventions in the prevention of GDM with the special role of MI. Results: Nutritional intervention and physical activity before and during pregnancy are mandatory in women affected by GDM. Moreover, the availability of insulin-sensitizers such as different forms of inositol has dramatically changed the scenario, allowing the treatment of several metabolic diseases, such as those related to glucose dysbalance. Although the optimal dose, frequency, and form of MI administration need to be further investigated, diet supplementation with MI appears to be an attractive alternative for the GDM prevention as well as for the reduction of GDM-related complications. Conclusion: More studies should be conducted to prove the most effective nutritional intervention in GDM. Regarding the potential effectiveness of MI, further evidence in multicenter, randomized controlled trials is needed to draw firm conclusions.


2021 ◽  
Author(s):  
Haowen Zhang ◽  
Ce Qi ◽  
Yuning Zhao ◽  
Mengyao Lu ◽  
Xinyue Li ◽  
...  

Gestational diabetes mellitus (GDM) may be related to intestinal mucosal damage and inflammation-induced dysbiosis of secretory IgA (SIgA) coated microbiota. SIgA coated L. reuteri can reduce the level of inflammation of GDM in vitro.


2021 ◽  
Vol 8 ◽  
Author(s):  
Mei Wang

There are two fairly common complications during pregnancy, i.e., gestational diabetes mellitus (GDM) and pre-eclampsia, which are independent, but are also closely linked in prevalence in pregnant women, with potential serious adverse consequences. IL-37 and IL-38, which belong to the IL-1 superfamily, participate in anti-inflammatory responses. Dysregulation of IL-37 and IL-38 has been observed in many auto-immune diseases. IL-37 is substantially reduced in the umbilical cords and placentas of GDM subjects, but IL-37 is significantly induced in the placentas of pre-eclampsia patients, suggesting there are differential regulatory roles of IL-37 in obstetrics, despite IL-37 being an anti-inflammatory mediator. Furthermore, IL-38 is substantially increased in the umbilical cords and placentas of GDM subjects, but minimal difference is observed in the placentas from pre-eclampsia patients. These data imply that IL-38 is also regulated independently within the diseased placentas. This review provides some insight for both basic scientists and medical practitioners to manage these patients effectively.


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