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Abstract
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.
Highlights
Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy, which causes more and more burden to public health due to its increasing incidence [1]
Besides increased levels of estrogen, progesterone, and cortisol during pregnancy, dysregulated placental immunity attributed to various inflammatory cells and their generated inflammation-related mediators in placenta can induce insulin resistance and lead to GDM, such as placental macrophages, dendritic cells, and Th1 cells [5, 6]
We have previously found miR657 is dysregulated in placenta and participates in GDM by regulating inflammatory response [13]
Summary
Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy, which causes more and more burden to public health due to its increasing incidence [1]. Both the GDM pregnant women and the infants are at an elevated risk of complications, such as gestational hypertension and preeclampsia for mothers and hyperbilirubinemia, hypocalcemia, and respiratory distress syndrome for babies [2, 3]. The diagnosis of GDM is often missed due to its complicated pathogenesis and lack of reliable biological markers for GDM screening and monitoring during pregnancy
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