Metformin exhibits its therapeutic effect in the treatment of pre-eclampsia via modulating the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways

Shu, Chen; Yan, Dongmei; Chen, Chen; Mo, Yanxiang; Wu, Linlin; Gu, Jishuang; Shah, Neelam; He, Junqi; Dong, Shuai

doi:10.1016/j.intimp.2019.105693

Cited by 21 publications

(15 citation statements)

References 31 publications

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“…46 An alternative possibility is that IL-27 mRNA induced by IFN plus R848-mRNA is not translated at all, maybe because it is subjected to microRNA-dependent regulatory controls. 47 The latter possibility might be in line with other findings observed in neutrophils incubated with R848 in combination with TNF . Accordingly, R848 plus TNF were found to additively induce the levels of EBI3 mRNA, but not those of EBI3 production, suggesting that regulatory mechanisms controlling also EBI3 translation or intracellular accumulation/release might take place in neutrophils.…”

Section: Discussionsupporting

confidence: 78%

“…It is therefore possible that the IL27A mRNA induced in IFNγ plus R848‐treated neutrophils is translated, but not released, because it is stored in intracellular compartments, similar to what was observed for instance in the case of CXCL8, 44 BAFF, 45 or TRAIL 46 . An alternative possibility is that IL‐27 mRNA induced by IFNγ plus R848‐mRNA is not translated at all, maybe because it is subjected to microRNA‐dependent regulatory controls 47 . The latter possibility might be in line with other findings observed in neutrophils incubated with R848 in combination with TNFα.…”

Section: Discussionmentioning

confidence: 72%

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Human neutrophils activated by TLR8 agonists, with or without IFNγ, synthesize and release EBI3, but not IL-12, IL-27, IL-35, or IL-39

Cassatella

Gardiman

Arruda‐Silva

et al. 2020

Journal of Leukocyte Biology

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The IL-12 family of cytokines plays crucial functions in innate and adaptive immunity. These cytokines include heterodimers sharing distinct (IL-12A, IL-23A, and IL-27A) with two (IL-12B and Epstein-Barr virus induced gene 3 [EBI3]) chains, respectively, IL-12 (IL-12B plus IL-12A) and IL-23 (IL-12B plus IL-23A) sharing IL-12B, IL-27 (EBI3 plus IL-27A), IL-35 (EBI3 plus IL-12A), and IL-39 (EBI3 plus IL-23A) sharing EBI3. In this context, we have recently reported that highly pure neutrophils incubated with TLR8 agonists produce functional IL-23. Previously, we showed that neutrophils incubated with LPS plus IFN for 20 h produce IL-12. Herein, we investigated whether highly pure, TLR8-activated, neutrophils produce EBI3, and in turn IL-27, IL-35, and IL-39, the IL-12 members containing it. We report that neutrophils incubated with TLR8 ligands, TNF and, to a lesser extent, LPS, produce and release remarkable amounts of EBI3, but not IL-27A, consequently excluding the possibility for an IL-27 production. We also report a series of unsuccessful experiments performed to investigate whether neutrophil-derived EBI3 associates with IL-23A to form IL-39. Furthermore, we show that neutrophils incubated with IFN in combination with either TLR8 or TLR4 ligands express/produce neither IL-12, nor IL-35, due to the inability of IFN , contrary to previous findings, to activate IL12A transcription. Even IL-27 was undetectable in supernatants harvested from IFN plus R848-treated neutrophils, although they were found to accumulate IL27A transcripts. Finally, by immunohistochemistry experiments, EBI3-positive neutrophils were found in discrete pathologies only, including diverticulitis, cholecystitis, Gorham disease, and Bartonella Henselae infection, implying a specific role of neutrophil-derived EBI3 in vivo.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 72%

Human neutrophils activated by TLR8 agonists, with or without IFNγ, synthesize and release EBI3, but not IL-12, IL-27, IL-35, or IL-39

Cassatella

Gardiman

Arruda‐Silva

et al. 2020

Journal of Leukocyte Biology

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“…H19, a lncRNA, is involved in the pathogenesis of several diseases, including lung cancer and pre-eclampsia (28,29). Although a previous study reported that the methylation of H19 differentially methylated regions is increased in the placental samples of SA cases (23), the role and underlying mechanism of H19 in SA are still largely unclear.…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA H19 regulates Bcl‑2, Bax and phospholipid hydroperoxide glutathione peroxidase expression in spontaneous abortion

Bai

Tang

2020

Exp Ther Med

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“… [ 150 ] miR-148a-5p/P28/miR-216-3p/EBI3 Down-regulated could up-regulate the expression of miR-148-5p/miR-216-3p and the expressions of subunits of IL-27, P28 and EBI3 were thus suppressed. [ 151 ] miRNAlet-7/the type III TGF-β receptor (TβR3) H19 repression decreases TGF-β signaling via the Par6/Smurf1/RhoA pathway activated by TβR3, leading to impaired migration and invasion of EVT cells. [ 152 ] upregulated PI3K/AKT/mTOR pathways LncRNA-H19 overexpression reduces cell viability but increases invasion and autophagy in trophoblast cells by enhancing phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathways.…”

Section: Lncrnas and Pementioning

confidence: 99%

Roles of noncoding RNAs in preeclampsia

Sun

Qin

Zhang

et al. 2021

Reprod Biol Endocrinol

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Preeclampsia (PE) is an idiopathic disease that occurs during pregnancy. It comprises multiple organ and system damage, and can seriously threaten the safety of the mother and infant throughout the perinatal period. As the pathogenesis of PE is unclear, there are few specific remedies. Currently, the only way to eliminate the clinical symptoms is to terminate the pregnancy. Although noncoding RNA (ncRNA) was once thought to be the “junk” of gene transcription, it is now known to be widely involved in pathological and physiological processes, including pregnancy-related disorders. Moreover, there is growing evidence that the unbalanced expression of specific ncRNA is involved in the pathogenesis of PE. In the present review, we summarize the expression patterns of ncRNAs, i.e., microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), and the functional mechanisms by which they affect the development of PE, and examine the clinical significance of ncRNAs as biomarkers for the diagnosis of PE. We also discuss the contributions made by genetic polymorphisms and epigenetic ncRNA regulation to PE. In the present review, we wish to explore and reinforce the clinical value of ncRNAs as noninvasive biomarkers of PE.

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Metformin exhibits its therapeutic effect in the treatment of pre-eclampsia via modulating the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways

Cited by 21 publications

References 31 publications

Human neutrophils activated by TLR8 agonists, with or without IFNγ, synthesize and release EBI3, but not IL-12, IL-27, IL-35, or IL-39

Human neutrophils activated by TLR8 agonists, with or without IFNγ, synthesize and release EBI3, but not IL-12, IL-27, IL-35, or IL-39

Long non‑coding RNA H19 regulates Bcl‑2, Bax and phospholipid hydroperoxide glutathione peroxidase expression in spontaneous abortion

Roles of noncoding RNAs in preeclampsia

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