MIF-mediated NF-κB signaling pathway regulates the pathogenesis of polycystic ovary syndrome in rats

He, Zhenlin; Wang, Yuelong; Li, Zhuan; Li, Yunxiu; Tang, Z-ouyin; Wu, Ze; Ma, Yanping

doi:10.1016/j.cyto.2021.155632

Cited by 19 publications

(10 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LPS is considered to have the effect of endotoxin, which can activate CD14/TLR4 receptors on the surface of immune cells and induce inflammatory response ( Festi et al., 2014 ; Hersoug et al., 2016 ; Nighot et al., 2019 ; Chang et al., 2021 ). Chronic low-grade inflammation is considered to be a key factor in the pathogenesis of PCOS ( Vrieze et al., 2010 ; Tremellen and Pearce, 2012 ; Crommen and Simon, 2017 ; Patel, 2018 ; Thackray, 2019 ; Abraham Gnanadass et al., 2021 ; He et al., 2021 ). Chang et al.…”

Section: Discussionmentioning

confidence: 99%

Modified Banxia Xiexin Decoction Ameliorates Polycystic Ovarian Syndrome With Insulin Resistance by Regulating Intestinal Microbiota

Zhao

Chen

Zheng

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

ObjectiveTo analyze the characteristics of the intestinal microbiota of polycystic ovarian syndrome with insulin resistance (PCOS-IR) and explore the possible mechanism of modified Banxia Xiexin Decoction in the treatment of PCOS-IR.MethodsA total of 17 specific pathogen-free (SPF) female Sprague–Dawley (SD) rats, aged 21 days, were selected and randomly divided into the control group (group Z, n = 6), model group (group M, n = 6), and treatment group (group A, n = 5). Letrozole combined with a high-fat diet was used to induce the PCOS-IR model. Rats in group A were treated with modified Banxia Xiexin Decoction for 2 weeks after the end of modeling; then the characteristics of reproductive, metabolic, inflammatory, and intestinal microbiota were compared among three groups.ResultsThe PCOS-IR model had an imbalance of intestinal microbiota, and the enriched microbiota was mainly class Coriobacteria, order Clostridiales, and genus Clostridium_sensu_stricto_1. Modified Banxia Xiexin Decoction can regulate the disorder of intestinal microbiota diversity, significantly increase the abundance of phyla Verrucomicrobiota Proteobacteria and genera Akkermansia and Blautia, and decrease the abundance of genus Clostridium_sensu_stricto_1.ConclusionGenus Clostridium_sensu_stricto_1 might be the pivotal pathogenic bacteria of PCOS-IR. Modified Banxia Xiexin Decoction may ameliorate PCOS-IR by regulating intestinal microbiota imbalance and improving metabolic disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

Modified Banxia Xiexin Decoction Ameliorates Polycystic Ovarian Syndrome With Insulin Resistance by Regulating Intestinal Microbiota

Zhao

Chen

Zheng

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Accumulation of macrophages can also result in an influx of a plethora of proinflammatory cytokines and chemokines (IL-1, IL-6, IL-10, IL-12, and TNF-α) into the circulatory system at the same time, leading to a state of systemic chronic low-grade inflammation ( 76 , 77 ). The macrophage M0 polarization translates to a pro-inflammatory M1 state, and then M1 stimulates the production of androgen and inhibits insulin sensitivity by producing TNF-α and IL-6 in PCOS ( 68 , 78 , 79 ). Mast cells could take part in immune regulation by a variety of cytokines.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Proteomics Reveals That a Prognostic Signature of the Endometrium of the Polycystic Ovary Syndrome Women Based on Ferroptosis Proteins

et al. 2022

View full text Add to dashboard Cite

ObjectiveWe aimed to study the relationship between ferroptosis proteins and reproductive outcomes of infertile patients with PCOS and construct the related prognostic model.MethodsThese endometrium samples of the study were collected from 33 women with PCOS and 7 control women with successful pregnancies at the Reproductive Center of Lanzhou University Second Hospital, September 2019 to September 2020. The 40 patients’ endometrium was identified the differentially expressed proteins (DEPs) using liquid chromatography tandem mass spectrometry. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) showed that the DEPs related pathways and functions between PCOS and controls. Subsequently, univariate Cox regression analysis and Lasso regression were used to identifying independent prognostic ferroptosis proteins, which were utilized to establish a prognostic model. Then the performance of the prognostic model was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). Then clinical data and prognostic model were used to predict the reproductive outcomes of PCOS patients by constructing the nomograms. Finally, we performed the single sample gene set enrichment analysis (ssGSEA) to explore the correlation between risk scores and immune status.ResultsA total of 5331 proteins were identified, 391 proteins were differentially expressed in the PCOS and controls. The KEGG analysis revealed that the ferroptosis pathway was significantly different between PCOS and controls. 5 ferroptosis proteins (GPX4, DPP4, G6PD, PCBP1, and PCBP2) prognostic model (FerSig) was constructed via Cox regression and Lasso regression. Patients were separated into high and low-risk groups according to the FerSig. Kaplan-Meier curve showed that patients in the low-risk group had much better reproductive outcomes than those in the high-risk group. The DCA showed that the risk score was an independent predictive factor for reproductive outcomes. Compared with clinical data, ROC curve analysis indicated the FerSig proteins as a potential diagnostic and prognostic factor in PCOS patients. Functional analysis revealed that the FerSig proteins and immune microenvironment were correlated to the prognosis of PCOS.ConclusionThe prognostic model focused on the FerSig proteins could predict the reproductive outcomes of PCOS patients with decreased endometrial receptivity, and provided theoretical basis for individualized treatment.

show abstract

“…It has been pointed out that the activated NF-κB signaling pathway might be one of the important factors in the pathogenesis of IR in PCOS. [ 20 , 21 ] Conversely, IR can also disrupt ovarian and uterine glucocorticoid receptor activation by regulating the NF-κB signaling pathway and then lead to PCOS. [ 22 ] Zhao, Y et al demonstrated that the expression of WNT5a in PCOS patients was significantly elevated, and the up-regulated expression of WNT5a in PCOS increases inflammation and oxidative stress predominantly via the PI3K/Akt/NF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Exploration of hub genes involved in PCOS using biological informatics methods

et al. 2022

View full text Add to dashboard Cite

Background: The aim of this study was to find underlying genes and their interaction mechanism crucial to the polycystic ovarian syndrome (PCOS) by analyzing differentially expressed genes (DEGs) between PCOS and non-PCOS subjects.Methods: Gene expression data of PCOS and non-PCOS subjects were collected from gene expression omnibus (GEO) database. GEO2R were used to calculating P value and logFC. The screening threshold of DEGs was P < .05 and | FC | ≥ 1.2. GO annotation and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis was performed by using DAVID (2021 Update). The protein-protein interaction (PPI) network of DEGs was constructed by using the STRING database, and the hub genes were recognized through Hubba plugin of Cytoscape software.Results: PCOS and non-PCOS subjects shared a total of 174 DGEs, including 14 upregulated and 160 downregulated genes. The GO biological processes enriched by DEGs mainly involved actin cytoskeleton organization, positive regulation of NF-κB signaling pathway, and positive regulation of canonical Wnt signaling pathway. The DEGs were significantly enriched in cytoplasm, nucleus and cytosol. Their molecular functions mainly focused on protein binding, calmodulin binding and glycerol-3-phosphate dehydrogenase activity. The PI3K/Akt signaling pathway and glycosaminoglycan biosynthesis were highlighted as critical pathways enriched by DEGs. 10 hub genes were screened from the constructed PPI network, of which EGF, FN1 and TLR4 were mainly enriched in the PI3K/Akt signaling pathway. Conclusion:In this study, a total of 174 DEGs and 10 hub genes were identified as new candidate targets for insulin resistance (IR) in PCOS individuals, which may provide a new direction for developing novel treatment strategies for PCOS.Abbreviations: BP = biological process, CC = cellular component, DAVID = database for annotation, visualization, and integrated discovery, DEGs = differentially expressed genes, GEO = gene expression omnibus, GO = gene ontology, KEGG = Kyoto encyclopedia of genes and genomes, MF = molecular function, PCOS = polycystic ovarian syndrome, PPI = protein-protein interaction.

show abstract

MIF-mediated NF-κB signaling pathway regulates the pathogenesis of polycystic ovary syndrome in rats

Cited by 19 publications

References 24 publications

Modified Banxia Xiexin Decoction Ameliorates Polycystic Ovarian Syndrome With Insulin Resistance by Regulating Intestinal Microbiota

Modified Banxia Xiexin Decoction Ameliorates Polycystic Ovarian Syndrome With Insulin Resistance by Regulating Intestinal Microbiota

Quantitative Proteomics Reveals That a Prognostic Signature of the Endometrium of the Polycystic Ovary Syndrome Women Based on Ferroptosis Proteins

Exploration of hub genes involved in PCOS using biological informatics methods

Contact Info

Product

Resources

About