Modulation of preeclampsia by the cholinergic anti-inflammatory pathway: Therapeutic perspectives

Wedn, Abdalla M.; El-Bassossy, Hany M.; Eid, Ali H.; El‐Mas, Mahmoud M.

doi:10.1016/j.bcp.2021.114703

Cited by 18 publications

(15 citation statements)

References 249 publications

(403 reference statements)

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“…sEng is involved in neutralizing TGF-β, inhibiting the binding between TGF-β and its TGF-β receptor, and inducing vasodilation and endothelial nitric oxide synthase (eNOS) activation. 28 , 29 BMP activates SMAD1/5/8 through BMP type I [activin A receptor type (ALK)1, 2, 3, and 6] and type II receptors. 30 Our research focused on the role BMPR2 plays in PE.…”

Section: Discussionmentioning

confidence: 99%

The MEG3 lncRNA promotes trophoblastic cell growth and invasiveness in preeclampsia by acting as a sponge for miR-21, which regulates BMPR2 levels

Liu

Zhang

et al. 2021

Eur J Histochem

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Preeclampsia (PE) is one of the leading causes of maternal morbidity and mortality in pregnant women. This study aimed to investigate the potential impact and regulatory mechanisms of bone morphogenetic protein receptor 2 (BMPR2) on the progression of PE. We obtained placental tissues from pregnant women with PE and normal pregnant women, and the results showed that BMPR2 was expressed at low levels in the tissue from PE women. Genetic knockdown of BMPR2 increased the proliferation and invasion of cultured trophoblast cells, whereas its overexpression reduced these characteristics. Bioinformatics analysis and luciferase reporter gene assays confirmed that BMPR2 is a direct target of miR-21. Overexpression of a miR-21 inhibitor promoted the growth and invasiveness of trophoblast cells, whereas the opposite results were observed for the miR-21 mimic. Furthermore, miR-21 was sponged by the lncRNA MEG3, and shRNA inhibition of MEG3 reduced trophoblast cell growth and invasiveness. miR-21 was upregulated in the tissues from PE women, whereas MEG3 was downregulated, and the two were negatively correlated. Collectively, this study demonstrates that the lncRNA MEG3 acts as a sponge for miR-21, which regulates BMPR2 expression and promotes trophoblast cell proliferation and invasiveness, thereby preventing the development of PE. These findings provide novel insight into a targeted therapy that could be used to treat or prevent the development of PE.

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Section: Discussionmentioning

confidence: 99%

The MEG3 lncRNA promotes trophoblastic cell growth and invasiveness in preeclampsia by acting as a sponge for miR-21, which regulates BMPR2 levels

Liu

Zhang

et al. 2021

Eur J Histochem

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“…The role of ferritin and iron dextran in exacerbating preeclampsia in an L-NAME-treated rat model (ROS), resulting in a maternal inflammatory response and multi-organ injuries (6). Although oxidative stress is regarded as one of the leading causes of atherosclerosis in PE, and the levels of lipid peroxides in the placenta were found to be altered in PE, the mechanism by which oxidative stress works in PE development has not been completely defined (7,8).…”

Section: Original Articlementioning

confidence: 99%

“…Previous studies have revealed that many factors contribute to the onset of PE, including disordered neovascularization, impaired spiral artery remodeling, and oxygen dysregulation ( 3 - 5 ). Placental hypoxia initiates the release of inflammatory cytokines and overproduction of reactive oxygen species (ROS), resulting in a maternal inflammatory response and multi-organ injuries ( 6 ). Although oxidative stress is regarded as one of the leading causes of atherosclerosis in PE, and the levels of lipid peroxides in the placenta were found to be altered in PE, the mechanism by which oxidative stress works in PE development has not been completely defined ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

The role of ferritin and iron dextran in exacerbating preeclampsia in an L-NAME-treated rat model

Zhu¹,

Jiang²,

Xia³

et al. 2022

Ann Transl Med

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Background Preeclampsia (PE) occurs in the second half of pregnancy and contributes to maternal and perinatal morbidity and mortality. Ferritin plays a key role in pregnancy, but the underlying mechanisms of its involvement in PE remain elusive. This study aimed to investigate the effects of ferritin concentrations and ferroptosis levels on PE rats at different stages of pregnancy. Methods A PE rat model was established by administering nitro-L-arginine methyl ester (L-NAME; 60 mg/kg/day, orally) between the 13th and 19th days of pregnancy. Iron dextran (ID) was used to induce ferroptosis, whereas deferoxamine (DFO) was used to prevent ferroptosis. Pathological changes in the placenta and vascular system were observed by hematoxylin and eosin (H&E) staining. Oxidative stress levels, blood pressure, and urine protein levels were assessed. Inflammatory cytokines and cellular ferritin (FER)-related proteins were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to assess apoptosis- and ferroptosis-related proteins. Results The data showed that L-NAME elevated blood pressure and urine protein levels in pregnant rats, while treatment with DFO-late and ID-early reduced them. Placental and vascular damage were ameliorated, and the levels of nitric oxide (NO), nitric oxide synthase (NOS), and superoxide dismutase (SOD) were increased. In contrast, the generation of reactive oxygen species (ROS), malonaldehyde (MDA), inflammatory factors, and FER-related proteins were suppressed, accompanied by reduced apoptosis- and increased ferroptosis-related proteins in the DFO-late group. Conclusions Our results suggested that decreased ferritin levels in early pregnancy or elevated ferritin levels in late pregnancy in an L-NAME–treated rat model accelerated ferroptosis and exacerbated PE symptoms.

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“…The cholinergic anti-inflammatory pathway is an important pathway through which the intestinal flora affect brain function, and is known as the bacterium-entero-brain axis. Cholinergic anti-inflammatory pathways could regulate inflammatory responses in central nervous system and the peripheral tissues ( Ertle et al, 2021 ; Melo et al, 2021 ; Wedn et al, 2021 ). The function of the central choline system is closely related to the higher functions of the brain, such as awakening, learning, memory, sleep, and sensorimotor functions.…”

Section: Introductionmentioning

confidence: 99%

Association Among the Gut Microbiome, the Serum Metabolomic Profile and RNA m6A Methylation in Sepsis-Associated Encephalopathy

Wang

Chen

et al. 2022

Front. Genet.

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Objective: To investigate the relationship among the gut microbiome, serum metabolomic profile and RNA m6A methylation in patients with sepsis-associated encephalopathy (SAE), 16S rDNA technology, metabolomics and gene expression validation were applied.Methods: Serum and feces were collected from patients with and without (SAE group and non-SAE group, respectively, n = 20). The expression of serum markers and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA), and blood clinical indicators were detected using a double antibody sandwich immunochemiluminescence method. The expression of RNA m6A regulator were checked by Q-RTPCR. The gut microbiome was analyzed by 16S rDNA sequencing and the metabolite profile was revealed by liquid chromatography-mass spectrometry (LC-MS/MS).Results: In the SAE group, the IL-6, ICAM-5 and METTL3 levels were significantly more than those in the non-SAE group, while the FTO levels were significantly decreased in the SAE group. The diversity was decreased in the SAE gut microbiome, as characterized by a profound increase in commensals of the Acinetobacter, Methanobrevibacter, and Syner-01 genera, a decrease in [Eubacterium]_hallii_group, while depletion of opportunistic organisms of the Anaerofilum, Catenibacterium, and Senegalimassilia genera were observed in both groups. The abundance of Acinetobacter was positively correlated with the expression of METTL3. The changes between the intestinal flora and the metabolite profile showed a significant correlation. Sphingorhabdus was negatively correlated with 2-ketobutyric acid, 9-decenoic acid, and l-leucine, and positively correlated with Glycyl-Valine [Eubacterium]_hallii_group was positively correlated with 2-methoxy-3-methylpyazine, acetaminophen, and synephrine acetonide.Conclusion: The gut microbiota diversity was decreased. The serum metabolites and expression of RNA m6A regulators in PBMC were significantly changed in the SAE group compared to the non-SAE group. The results revealed that serum and fecal biomarkers could be used for SAE screening.

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Modulation of preeclampsia by the cholinergic anti-inflammatory pathway: Therapeutic perspectives

Cited by 18 publications

References 249 publications

The MEG3 lncRNA promotes trophoblastic cell growth and invasiveness in preeclampsia by acting as a sponge for miR-21, which regulates BMPR2 levels

The MEG3 lncRNA promotes trophoblastic cell growth and invasiveness in preeclampsia by acting as a sponge for miR-21, which regulates BMPR2 levels

The role of ferritin and iron dextran in exacerbating preeclampsia in an L-NAME-treated rat model

Association Among the Gut Microbiome, the Serum Metabolomic Profile and RNA m6A Methylation in Sepsis-Associated Encephalopathy

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