IL-27 Mediates Pro-Inflammatory Effects via the ERK Signaling Pathway During Preterm Labor

Huang, Dongni; Ran, Yuxin; Liu, Zheng; He, Jie; Yin, Ning; Qi, Hongbo

doi:10.3389/fimmu.2021.709229

Cited by 7 publications

(10 citation statements)

References 58 publications

(62 reference statements)

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“…miR-132-3p was also shown to be involved in the development of preeclampsia by promoting trophoblast cells viability and invasiveness, and inhibiting apoptosis via targeting DAPK-1 [21]. There is growing body of evidence indicating that the activation of ERK, p38, JNK, NF-κB, and STAT3 signaling pathways participate in the process of initiation parturition and preterm labor, particularly in inflammatory and hormonal aspects [32][33][34][35]. The actions of miR-132-3p are closely related to these signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

miR-132-3p Modulates DUSP9-Dependent p38/JNK Signaling Pathways to Enhance Inflammation in the Amnion Leading to Labor

Zhong

Liu

Zheng

et al. 2022

IJMS

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Labor is a process of inflammation and hormonal changes involving both fetal and maternal compartments. MicroRNA-132-3p (miR-132-3p) has been reported to be involved in the development of inflammation-related diseases. However, little is known about its potential role in labor onset. This study aimed to explore the mechanism of miR-132-3p in amnion for labor initiation. In the mouse amnion membranes, the expression of miR-132-3p was found to increase gradually during late gestation. In human amniotic epithelial cell line (WISH), upregulation of miR-132-3p was found to increase proinflammatory cytokines and cyclooxygenase 2 (COX2) as well as prostaglandin E2 (PGE2), which was suppressed by miR-132-3p inhibitor. Dual-specificity phosphatase 9 (DUSP9) was identified as a novel target gene of miR-132-3p, which could be negatively regulated by miR-132-3p. DUSP9 was present in the mouse amnion epithelial cells, with a decrease in its abundance at 18.5 days post coitum (dpc) relative to 15.5 dpc. Silencing DUSP9 was found to facilitate the expression of proinflammatory cytokines and COX2 as well as PGE2 secretion in WISH cells, which could be attenuated by p38 inhibitor SB203580 or JNK inhibitor SP600125. Additionally, intraperitoneal injection of pregnant mice with miR-132-3p agomir not only caused preterm birth, but also promoted the abundance of COX2 as well as phosphorylated JNK and p38 levels, and decreased DUSP9 level in mouse amnion membranes. Collectively, miR-132-3p might participate in inflammation and PGE2 release via targeting DUSP9-dependent p38 and JNK signaling pathways to cause preterm birth.

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Section: Discussionmentioning

confidence: 99%

miR-132-3p Modulates DUSP9-Dependent p38/JNK Signaling Pathways to Enhance Inflammation in the Amnion Leading to Labor

Zhong

Liu

Zheng

et al. 2022

IJMS

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“…LPS is widely used to establish the cell model of PTB. 19,23,24 We then investigated the potential effect of miR-26a-5p on TRPC3 expression in a cell model of PTB. The results demonstrated that the expression of TRPC3 was remarkably upregulated in LPS-stimulated cells (a cell model of PTB) compared to the control cells.…”

Section: Overexpression Of Mir-26a-5p Decreases Trpc3 Levels In Lps-s...mentioning

confidence: 99%

“…22 LPS is widely used to establish an in vitro model of PTB. 19,23,24 In our study, we investigated the role of miR-26a-5p/TRPC3 axis in PTB using this model.…”

mentioning

confidence: 99%

MiRNA‐26a‐5p inhibits preterm labor initiation by targeting and regulating TRPC3 ion channel protein expression

Chen,

Liu,

Cui

et al. 2023

Environmental Toxicology

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The incidence of preterm birth (PTB) is increasing annually worldwide, leading to various health problems or even fetal deaths. Our previous work demonstrated the activation of transient receptor potential cation channel subfamily C 3 (TRPC3) in mice with PTB, and its activation could promote inward flow of calcium ions and uterine smooth muscle (USM) contraction via regulation of Cav3.2, Cav3.1, and Cav1.2. However, the upstream regulators of TRPC3 and its mechanisms remain unknown. In the present study, the binding of miR‐26a‐5p to the 3′ untranslated region of TRPC3 was predicted by bioinformatics databases (TargetScanHuman and starBase v3.0) and confirmed by a dual‐luciferase assay. MiR‐26a‐5p was downregulated, while TRPC3 was upregulated in the USM tissues of patients with PTB compared to people without PTB. The results showed that miR‐26a‐5p mimic transfection markedly reduced TRPC3 expression in LPS‐stimulated USM cells. Additionally, miR‐26a‐5p regulated intracellular Ca2+ levels in USM cells by targeting TRPC3. Furthermore, miR‐26a‐5p inhibited the CPI17/PKC/PLCγ signaling pathway and reduced the expression of Cav3.2, Cav3.1, and Cav1.2. In conclusion, miR‐26a‐5p regulated the initiation of PTB by targeting TRPC3 and regulating intracellular Ca2+ levels. This study provides a promising diagnostic biomarker and therapeutic target for PTB.

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“…They have been used to validate some compounds potentially preventing preterm delivery, such as naloxone, progesterone or corticoids (Romero et al, 2006;Arenas-Hernandez et al, 2019;Green and Arck, 2020;Galaz et al, 2021;Ginsberg et al, 2021). Lipopolysaccharide (LPS) stimulated infection is one of the most popular models to study inflammatory preterm birth, probably because of its low-cost and effectivity (Huang et al, 2021). Within this model, several inflammatory pathways and features have been profoundly studied during preterm labor, such as the implication of Interleukin-27 (IL-27) in the activation of extracellular signal-regulated kinases (ERK) pathway, which ultimately origins preterm labor (Huang et al, 2021).…”

Section: Lessons From Murine Models: Inflammatory Vs Non-inflammatory...mentioning

confidence: 99%

“…Lipopolysaccharide (LPS) stimulated infection is one of the most popular models to study inflammatory preterm birth, probably because of its low-cost and effectivity (Huang et al, 2021). Within this model, several inflammatory pathways and features have been profoundly studied during preterm labor, such as the implication of Interleukin-27 (IL-27) in the activation of extracellular signal-regulated kinases (ERK) pathway, which ultimately origins preterm labor (Huang et al, 2021). In this model, interventions with probiotics, such as Lentilactobacillus kefiri (Lk48), can impair the inflammatory process and diminish the rate of neonatal death (Ventimiglia et al, 2021).…”

Section: Lessons From Murine Models: Inflammatory Vs Non-inflammatory...mentioning

confidence: 99%

Preterm Delivery: Microbial Dysbiosis, Gut Inflammation and Hyperpermeability

et al. 2022

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Preterm birth is one of the main health problems encountered in the neonatal period, especially because it is also the first cause of death in the critical 1st month of life and the second in children under 5 years of age. Not only preterm birth entails short term health risks due to low weight and underdeveloped organs, but also increases the risk of suffering from non-transmissible diseases in the long term. To date, it is known that medical conditions and lifestyle factors could increase the risk of preterm birth, but the molecular mechanisms that control this process remain unclear. Luteolysis, increased inflammation or oxidative stress have been described as possible triggers for preterm birth and, in some cases, the cause of dysbiosis in preterm neonates. Several murine models have been developed to shed light into the mechanistic of preterm birth but, for the most part, are inflammation-based labor induction models and the offspring health readouts are mainly limited to survival and weight. Using a set of SWISS-CD1 mice born prematurely we analyzed inflammation and gut permeability parameters compared with term pups at weaning age. Overall, preterm mice presented higher systemic inflammation and gastrointestinal tract permeability. In this perspective article, we discuss the recent discoveries on preterm birth and the necessity of non-inflammatory murine models to really understand these phenotypes and be able to design strategies to prevent the sequels of this traumatic event in neonates.

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IL-27 Mediates Pro-Inflammatory Effects via the ERK Signaling Pathway During Preterm Labor

Cited by 7 publications

References 58 publications

miR-132-3p Modulates DUSP9-Dependent p38/JNK Signaling Pathways to Enhance Inflammation in the Amnion Leading to Labor

miR-132-3p Modulates DUSP9-Dependent p38/JNK Signaling Pathways to Enhance Inflammation in the Amnion Leading to Labor

MiRNA‐26a‐5p inhibits preterm labor initiation by targeting and regulating TRPC3 ion channel protein expression

Preterm Delivery: Microbial Dysbiosis, Gut Inflammation and Hyperpermeability

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