BACKGROUND Obesity and type 2 diabetes mellitus(T2DM)are frequent co-occurring disorders that affect regular metabolic functions.Obesity has also been linked to an inc-reased risk of developing diabetes.Obesity and di...BACKGROUND Obesity and type 2 diabetes mellitus(T2DM)are frequent co-occurring disorders that affect regular metabolic functions.Obesity has also been linked to an inc-reased risk of developing diabetes.Obesity and diabetes are on the rise,increa-sing healthcare costs and raising mortality rates.Research has revealed that the expression profile of microRNAs(miRNAs)changes as diabetes progresses.Fur-thermore,vitamin D may have an anti-obesity effect and inverse association with body weight and body mass index(BMI).Low vitamin D levels do not solely cause obesity,which could be a factor in the etiology of T2DM.METHODS This study included 210 participants,of which,82 were obese(BMI>30 kg/m2)without T2DM,28 were obese with T2DM,and 100 were healthy controls.BMI was evaluated and both fasting and postprandial blood glucose were used to confirm T2DM.Exosomal miRNA-200a and miRNA-200b expression were analyzed using real-time PCR using Taqman probes,and vitamin-D levels were evaluated using an electrochemiluminescence-based immunoassay technique.All data analyses were performed using SPSS 20.0 and GraphPad Prism 5 software.RESULTS Overall,a 2.20-and 4.40-fold increase in miRNA-200a and miRNA-200b expression was observed among participants compared to healthy controls.MiRNA-200a and miRNA-200b expression among obese participants increased 2.40-fold and 3.93-fold,respectively,while in obese T2DM participants these values were 2.67-fold,and 5.78-fold,respectively,and these differences were found to be statistically significant(P=0.02)(P<0.0001).Obese participants showed a vitamin D level of 34.27 ng/mL,while in obese-T2DM participants vitamin D level was 22.21 ng/mL(P<0.0001).Vitamin D was negatively correlated with miRNA-200a(r=-0.22,P=0.01)and miRNA-200b(r=-0.19,P=0.04).MiRNA-200a sensitivity was 75%,and specificity was 57%,with a cutoff value of 2.07-fold.MiRNA-200b sensitivity was 75%,and specificity was 71%with a cutoff value of 4.12-fold,suggesting that miRNA-200a and miRNA-200b with an increased expression of 2.07-and 4.12-fold could be predictive indicators for the risk of diabetes in obese participants.CONCLUSION MiRNA-200a and miRNA-200b were higher in diabetic obese participants vs non-diabetic obese participants,and insufficient vitamin D levels in obese T2DM participants may be involved in poor clinical outcome.展开更多
miRNAs play important roles in the post-transcriptional regulation of most transcripts and control several biological processes. We have shown that miR-200b regulates VEGF and miR-146a regulates ECM （extracellular ma...miRNAs play important roles in the post-transcriptional regulation of most transcripts and control several biological processes. We have shown that miR-200b regulates VEGF and miR-146a regulates ECM （extracellular matrix） protein, FN （fibronectin） production. We examined the effects of these two miRNAs in wound healing in vitro and in animals with or without diabetes. Microvascular ECs （endothelial cells） with or without miR inhibitor （antagomir） transfection were tested for VEGF and FN production. Scratch assays and angiogenesis assays were performed. Wounds in the back of mice with or without streptozotocin-induced diabetes were treated with antagomirs alone or in combinations. The wounds were measured and tissues were examined for mRNAs, proteins and miRNAs and examined histologically. In the ECs, miR-200b or miR-146a inhibitors increased VEGF and FN production, cell migration and tube formation. Wound healing in the animals, along with increased production of specific proteins were accelerated by miR-200b or miR-146a inhibitor treatment and was pronounced when these two were combined In diabetes, although delayed, similar patterns were seen. These results indicated that combination of miR-146a and miR-200b inhibitor treatment is useful in wound healing both in normal and in diabetic conditions, miRNA mediated wound healing may potentially constitute a novel therapeutic approach.展开更多
基金Supported by The Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia,for funding this research work through the project number ISP-24.,Jazan University,Jazan 82817,Saudi Arabia.
文摘BACKGROUND Obesity and type 2 diabetes mellitus(T2DM)are frequent co-occurring disorders that affect regular metabolic functions.Obesity has also been linked to an inc-reased risk of developing diabetes.Obesity and diabetes are on the rise,increa-sing healthcare costs and raising mortality rates.Research has revealed that the expression profile of microRNAs(miRNAs)changes as diabetes progresses.Fur-thermore,vitamin D may have an anti-obesity effect and inverse association with body weight and body mass index(BMI).Low vitamin D levels do not solely cause obesity,which could be a factor in the etiology of T2DM.METHODS This study included 210 participants,of which,82 were obese(BMI>30 kg/m2)without T2DM,28 were obese with T2DM,and 100 were healthy controls.BMI was evaluated and both fasting and postprandial blood glucose were used to confirm T2DM.Exosomal miRNA-200a and miRNA-200b expression were analyzed using real-time PCR using Taqman probes,and vitamin-D levels were evaluated using an electrochemiluminescence-based immunoassay technique.All data analyses were performed using SPSS 20.0 and GraphPad Prism 5 software.RESULTS Overall,a 2.20-and 4.40-fold increase in miRNA-200a and miRNA-200b expression was observed among participants compared to healthy controls.MiRNA-200a and miRNA-200b expression among obese participants increased 2.40-fold and 3.93-fold,respectively,while in obese T2DM participants these values were 2.67-fold,and 5.78-fold,respectively,and these differences were found to be statistically significant(P=0.02)(P<0.0001).Obese participants showed a vitamin D level of 34.27 ng/mL,while in obese-T2DM participants vitamin D level was 22.21 ng/mL(P<0.0001).Vitamin D was negatively correlated with miRNA-200a(r=-0.22,P=0.01)and miRNA-200b(r=-0.19,P=0.04).MiRNA-200a sensitivity was 75%,and specificity was 57%,with a cutoff value of 2.07-fold.MiRNA-200b sensitivity was 75%,and specificity was 71%with a cutoff value of 4.12-fold,suggesting that miRNA-200a and miRNA-200b with an increased expression of 2.07-and 4.12-fold could be predictive indicators for the risk of diabetes in obese participants.CONCLUSION MiRNA-200a and miRNA-200b were higher in diabetic obese participants vs non-diabetic obese participants,and insufficient vitamin D levels in obese T2DM participants may be involved in poor clinical outcome.
文摘miRNAs play important roles in the post-transcriptional regulation of most transcripts and control several biological processes. We have shown that miR-200b regulates VEGF and miR-146a regulates ECM （extracellular matrix） protein, FN （fibronectin） production. We examined the effects of these two miRNAs in wound healing in vitro and in animals with or without diabetes. Microvascular ECs （endothelial cells） with or without miR inhibitor （antagomir） transfection were tested for VEGF and FN production. Scratch assays and angiogenesis assays were performed. Wounds in the back of mice with or without streptozotocin-induced diabetes were treated with antagomirs alone or in combinations. The wounds were measured and tissues were examined for mRNAs, proteins and miRNAs and examined histologically. In the ECs, miR-200b or miR-146a inhibitors increased VEGF and FN production, cell migration and tube formation. Wound healing in the animals, along with increased production of specific proteins were accelerated by miR-200b or miR-146a inhibitor treatment and was pronounced when these two were combined In diabetes, although delayed, similar patterns were seen. These results indicated that combination of miR-146a and miR-200b inhibitor treatment is useful in wound healing both in normal and in diabetic conditions, miRNA mediated wound healing may potentially constitute a novel therapeutic approach.
