A MicroRNA Signature in Gestational Diabetes Mellitus Associated with Risk of Macrosomia

Li, Jiandong; Song, Liping; Zhou, Ling; Wu, Jiaoxiang; Sheng, Chunjie; Chen, Huiming; Liu, Yanjun; Gao, Shan; Huang, Wenlin

doi:10.1159/000430349

Cited by 108 publications

(97 citation statements)

References 23 publications

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“…MiRNAs are small endogenous non-coding RNAs (18-25 nucleotides in length) that negatively regulate gene expression through incomplete base-pairing to the 3ʹ untranslated region (3ʹ-UTR) of target mRNAs [5][6][7][8][9]. Increasing evidence suggests that miRNAs play a role in the regulation of diverse biological and pathological processes, such as developmental timeline, organogenesis, apoptosis, cell proliferation and differentiation [10,11].…”

Section: Introductionmentioning

confidence: 99%

MiR-27a is Essential for the Shift from Osteogenic Differentiation to Adipogenic Differentiation of Mesenchymal Stem Cells in Postmenopausal Osteoporosis

Pan²,

Chen³

et al. 2016

Cell Physiol Biochem

100

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Background/Aims: Osteoporosis is a progressive bone disease characterized by a decrease in bone mass and density, which results in an increased risk of fractures. Mesenchymal stem cells (MSCs) are progenitor cells that can differentiate into osteoblasts, osteocytes and adipocytes in bone and fat formation. A reduction in the differentiation of MSCs into osteoblasts contributes to the impaired bone formation observed in osteoporosis. MicroRNAs (miRNAs) play a regulatory role in osteogenesis and MSC differentiation. MiR-27a has been reported to be down-regulated in the development of osteoporosis and during adipogenic differentiation. Methods: In this study, a miRNA microarray analysis was used to investigate expression profiles of miRNA in the serum of osteoporotic patients and healthy controls and this data was validated by quantitative real-time PCR (qRT-PCR). MSCs isolated from human and mice with miR-27a inhibition or overexpression were induced to differentiate into osteoblasts or adipocytes. TargetScan and PicTar were used to predict the target gene of miR-27a. The mRNA or protein levels of several specific proteins in MSCs were detected using qRT-PCR or western blot analysis. Ovariectomized mice were used as in vivo model of human postmenopausal osteoporosis for bone mineral density measurement, micro-CT analysis and histomorphometric analysis. Results: Here, we analyzed the role of miR-27a in bone metabolism. Microarray analysis indicated that miR-27a expression was significantly reduced in osteoporotic patients. Analysis on MSCs derived from patients with osteoporosis indicated that osteoblastogenesis was reduced, whereas adipogenesis was increased. MSCs that had undergone osteoblast induction showed a significant increase in miR-27a expression, whereas cells that had undergone adipocyte induction showed a significant decrease in miR-27a expression, indicating that miR-27a was essential for MSC differentiation. We demonstrated that myocyte enhancer factor 2 c (Mef2c), a transcription factor, was the direct target of miR-27a using a dual luciferase assay. An inverse relationship between miR-27a expression and Mef2c expression in osteoporotic patients was shown. Silencing of miR-27a decreased bone formation, confirming the role of miR-27a in bone formation in vivo. Conclusion: In summary, miR-27a was essential for the shift of MSCs from osteogenic differentiation to adipogenic differentiation in osteoporosis by targeting Mef2c.

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Section: Introductionmentioning

confidence: 99%

MiR-27a is Essential for the Shift from Osteogenic Differentiation to Adipogenic Differentiation of Mesenchymal Stem Cells in Postmenopausal Osteoporosis

Pan²,

Chen³

et al. 2016

Cell Physiol Biochem

100

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“…MicroRNAs play important functions in the regulation of gene expression by targeting mRNA to affect its stability and translation [35]. Evidence has shown that the levels of APP and BACE1 protein are increased in the cortex and hippocampus after CBH in rats.…”

Section: Discussionmentioning

confidence: 99%

MiR-9 Regulates the Expression of BACE1 in Dementia Induced by Chronic Brain Hypoperfusion in Rats

Xie¹,

Zhao

Zhou

et al. 2017

Cell Physiol Biochem

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Background/Aims: MicroRNA-9 (miR-9) plays important roles in nervous system diseases such as glioblastoma and neurodegenerative disorders. However, how miR-9 contributes to dementia requires further study. In this study, we evaluated the role of miR-9 in dementia and the molecular mechanisms underlying its effects. Methods: A rat model of dementia was created by occlusion of the bilateral common carotid artery (2VO) for 8 weeks. Learning and memory were assessed using the Morris Water Maze (MWM). MicroRNA expression profiling was performed according to a protocol provided by LC Sciences, and quantitative real-time PCR (qRT-PCR) was used to detect the level of miR-9. Transmission electron microscopy (TEM) and hematoxylin-eosin (HE) staining were used to assess pathological changes in brain tissue. Western blot and immunofluorescence were employed to detect the expression of β-site APP cleaving enzyme 1 (BACE1) and c-AMP response element-binding protein (CREB). Results: Learning and memory were significantly impaired in 2VO rats, and these changes were accompanied by neuronal loss and glial activation in brain tissues. miR-9 was greatly upregulated in both the hippocampus and cortex of rats following 2VO. Knockdown of endogenous miR-9 via lentiviral vector-mediated delivery of its antisense molecule (lenti-pre-AMO-miR-9) reduced the vulnerability to dementia, reversed the increase in BACE1 expression, and ameliorated the reduction in CREB expression triggered by 2VO. BACE1 protein levels were significantly increased, but CREB protein levels were significantly decreased in the presence of miR-9 in cultured neonatal rat neurons (NRNs). AMO-miR-9 rescued the upregulation of BACE1 and downregulation of CREB elicited by miR-9 in rats. Dual luciferase assay experiments showed that overexpression of miR-9 inhibited the expression of CREB by targeting its 3’UTR domain. CREB protein was downregulated by miR-9 overexpression which was reversed by miR-9 inhibition in cultured NRNs. TEM imaging showed that miR-9 caused damage to NRNs, which was reversed by addition of AMO-miR-9. Conclusion: We conclude that miR-9 plays an important role in regulating the process of dementia induced by 2VO in rats by increasing BACE1 expression via downregulation of CREB.

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“…insulin secretion [49,50]. Altered microRNA expression has been detected in some pathologies, including GDM in which the altered microRNA signature may contribute to macrosomia in the offspring [51]. Given that BM is rich in microRNAs and that those components are transmitted to the breastfed infant via the digestive tract [52,53], it would be interesting to characterize microRNA content of GDMBM in order to better understand the effect of breastfeeding on growth of children born from mothers with GDM.…”

Section: Gestational Diabetes Mellitus and Breast Milk Compositionmentioning

confidence: 99%

Postnatal Prevention of Childhood Obesity in Offspring Prenatally Exposed to Gestational Diabetes mellitus: Where Are We Now

Dugas¹,

Perron²,

Kearney³

et al. 2017

Obes Facts

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Children exposed to gestational diabetes mellitus (GDM) in utero are at high risk of developing many health problems such as obesity. There is an urgent need to find new strategies to prevent obesity development among high-risk populations such as those children. Accordingly, the aim of this review was to summarize current knowledge on the postnatal prevention of childhood obesity in offspring born from mothers with GDM. Specifically, this review addresses the impact of breastfeeding, complementary feeding practices as well as dietary intake and physical activity during childhood on obesity risk of children exposed to GDM in utero. Furthermore, breast milk composition of diabetic mothers and its potential impact on growth is discussed. According to the available literature, breastfeeding may reduce obesity risk in children exposed to GDM in utero but a longer duration seems necessary to achieve its protective effect against obesity. Detailed analysis of breast milk composition of mothers with GDM will be necessary to fully understand the relationship between breastfeeding and obesity in this specific population. This review highlights the need for more studies addressing the impact of complementary feeding practices and lifestyle habits during childhood on obesity risk of children exposed to GDM in utero.

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A MicroRNA Signature in Gestational Diabetes Mellitus Associated with Risk of Macrosomia

Cited by 108 publications

References 23 publications

MiR-27a is Essential for the Shift from Osteogenic Differentiation to Adipogenic Differentiation of Mesenchymal Stem Cells in Postmenopausal Osteoporosis

MiR-27a is Essential for the Shift from Osteogenic Differentiation to Adipogenic Differentiation of Mesenchymal Stem Cells in Postmenopausal Osteoporosis

MiR-9 Regulates the Expression of BACE1 in Dementia Induced by Chronic Brain Hypoperfusion in Rats

Postnatal Prevention of Childhood Obesity in Offspring Prenatally Exposed to Gestational Diabetes mellitus: Where Are We Now

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