S100‐A9 protein in exosomes derived from follicular fluid promotes inflammation via activation of NF‐κB pathway in polycystic ovary syndrome

Li, Han; Huang, Xin; Chang, Xinwen; Yao, Julei; He, Qizhi; Shen, Zhijun; Ji, Yao; Wang, Kai

doi:10.1111/jcmm.14642

Cited by 75 publications

(69 citation statements)

References 59 publications

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“…p < 0.05 (*) was considered significant. The PPI network of DEGs with combined score > 0.7 was built by STRING v11.0 and visualized by Cytoscape v3.7.2 [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of Milk Fat Metabolism-Related Pathways of the Bovine Mammary Gland during Mid and Late Lactation and Functional Verification of the ACSL4 Gene

Fan

Han

et al. 2020

Genes

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The concentration of bovine milk fat changes regularly with lactation stages. In particular, milk fat percentage is higher in late lactation than mid lactation. Furthermore, milk fat composition is highly subject to a few genes. Thus, transcriptome sequencing was performed to explore the expression patterns of differentially-expressed genes (DEGs) in the parenchymal mammary gland of Holstein dairy cows between mid and late lactation. The 725 DEGs were screened (fold change > 2 and p-value < 0.05), and the peroxisome proliferator-activated receptor (PPAR) signaling pathway associated with lipid synthesis had a significant variation between the two periods (p-value < 0.05). The activation of the PPAR signal pathway may a key factor in the increasing of milk fat content in late lactation compared to mid lactation. Acyl-CoA synthetase long-chain family member 4 (ACSL4), a member of the PPAR signaling pathway, was upregulated in late lactation compared to mid lactation (p < 0.05). ACSL4 catalyzes the activation of long-chain fatty acids for cellular lipid synthesis. However, it remains uncertain that the molecular mechanism of milk fat synthesis is regulated by ACSL4 in dairy cows. Subsequently, the function verification of ACSL4 was performed in bovine mammary epithelial cells (BMECs). The upregulated expression of ACSL4 was accompanied by the increase of the concentration of intracellular triglycerides, whereas knockdown of ACSL4 decreased the concentration of intracellular triglycerides, which demonstrated that ACSL4 plays an important role in modulating milk fat synthesis. In conclusion, the results displayed that ACSL4 expression regulates triglyceride metabolism in ruminant mammary cells.

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“…p < 0.05 (*) was considered significant. The PPI network of DEGs with combined score > 0.7 was built by STRING v11.0 and visualized by Cytoscape v3.7.2 [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of Milk Fat Metabolism-Related Pathways of the Bovine Mammary Gland during Mid and Late Lactation and Functional Verification of the ACSL4 Gene

Fan

Han

et al. 2020

Genes

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“…They demonstrated that EVs released from polymorphonuclear leukocytes by healthy volunteers could induce endothelial cells to produce cytokines and chemokines in vitro . In follicular fluids of PCOS women, Li et al (2019) used a tandem mass tag quantitative proteomic approach and found that follicular fluid exosomes of both normal and PCOS samples contained S100 calcium-binding protein A9 (S100-A9). S100-A9 expression was greater in the follicular fluid exosomes of PCOS women and enhanced inflammation and disrupted steroidogenesis by activating the nuclear factor kappa B (NF-κB) signaling pathway.…”

Section: Extracellular Vesicles and Polycystic Ovary Syndromementioning

confidence: 99%

“…In basic research, on the one hand, EVs contribute to disease pathophysiology. EVs and cargos include protein, miRNAs and lncRNAs that promote the development of the disease by influencing inflammation, angiogenesis, steroidogenesis and macrophage phagocytic ability ( Mesri and Altieri, 1998 ; Boilard et al, 2010 ; Harp et al, 2016 ; Munros et al, 2017 ; Gomes de Andrade et al, 2018 ; Khalaj et al, 2019 ; Li et al, 2019 ; Qiu et al, 2019 ; Sun et al, 2019 ). This effect may be mediated by the NF-κB signaling pathway ( Li et al, 2019 ; Zhang et al, 2019 ).…”

Section: Extracellular Vesicles Application In Clinical and Basic Resmentioning

confidence: 99%

“…EVs and cargos include protein, miRNAs and lncRNAs that promote the development of the disease by influencing inflammation, angiogenesis, steroidogenesis and macrophage phagocytic ability ( Mesri and Altieri, 1998 ; Boilard et al, 2010 ; Harp et al, 2016 ; Munros et al, 2017 ; Gomes de Andrade et al, 2018 ; Khalaj et al, 2019 ; Li et al, 2019 ; Qiu et al, 2019 ; Sun et al, 2019 ). This effect may be mediated by the NF-κB signaling pathway ( Li et al, 2019 ; Zhang et al, 2019 ). On the other hand, EVs can also alleviate disease development ( Wu et al, 2018 ; Liu et al, 2019 ; Mobarak et al, 2019 ; Yoshida et al, 2019 ; Zhao et al, 2019 ).…”

Section: Extracellular Vesicles Application In Clinical and Basic Resmentioning

confidence: 99%

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Extracellular Vesicles: Recent Developments in Aging and Reproductive Diseases

Liu

Shen

Zhang

et al. 2020

Front. Cell Dev. Biol.

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Extracellular vesicles (EVs), present in cell culture media and several body fluids, play a prominent role in intercellular communication under physiological and pathological conditions. We performed a systematic literature search to review evidence regarding the existence, composition, and release of different EVs, as well as the biomarkers, cargos, and separation methods. We also reviewed the potential of EVs to transport cargos and alter the function and phenotype of recipient cells associated with aging and reproductive diseases, including polycystic ovary syndrome and endometriosis. In aging, EVs promote inflammatory reactions and offsetting the occurrence of aging. In the polycystic ovary syndrome and endometriosis, EVs and their cargos are involved in the occurrence of diseases, therapeutic strategies, and perform as non-invasive biomarkers. As the study of EVs is still in the early stages, it is not surprising that most of the current literature only describes their possible roles.

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“…However, no comprehensive analysis of the bovine ffEV protein cargo has yet been performed. In contrast, the protein cargo of ffEVs has been assessed in equine and human ffEVs, and 73 and 662 proteins were identified, respectively ( 20 , 29 ). Moreover, a comparison of the abundance of ffEV proteins in control and polycystic ovary syndrome ovaries could potentially identify potential markers of oocyte quality ( 29 ).…”

Section: Introductionmentioning

confidence: 99%

Protein Cargo of Extracellular Vesicles From Bovine Follicular Fluid and Analysis of Their Origin From Different Ovarian Cells

et al. 2020

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Follicular fluid (FF) fills the interior portion of the ovarian antral follicle and provides a suitable microenvironment for the growth of the enclosed oocyte through molecular factors that originate from plasma and the secretions of follicular cells. FF contains extracellular nanovesicles (ffEVs), including 30–100-nm membrane-coated exosomes, which carry different types of RNA, proteins, and lipids and directly influence oocyte competence to develop embryo. In the present study, we aimed to characterize the protein cargo of EVs from the FF of 3–6-mm follicles and uncover the origins of ffEVs by assessing expression levels of corresponding mRNAs in bovine follicular cells and oocyte and cell proteomes. Isolated exosome-like ffEVs were 53.6 + 23.3 nm in size and could be internalized by cumulus-oocyte complex. Proteomes of ffEVs and granulosa cells (GC) were assessed using nanoflow liquid chromatography coupled with high-resolution tandem mass spectrometry after the gel fractionation of total proteins. In total, 460 protein isoforms corresponding to 322 unique proteins were identified in ffEVs; among them, 190 were also identified via GC. Gene Ontology terms related to the ribosome, protein and RNA folding, molecular transport, endocytosis, signal transduction, complement and coagulation cascades, apoptosis, and developmental biology pathways, including PI3K-Akt signaling, were significantly enriched features of ffEV proteins. FfEVs contain numerous ribosome and RNA-binding proteins, which may serve to compact different RNAs to regulate gene expression and RNA degradation, and might transfer ribosomal constituents to the oocyte. Majority of genes encoding ffEV proteins expressed at different levels in follicular cells and oocyte, corroborating with numerous proteins, which were reported in bovine oocyte and cumulus cells in other studies thus indicating possible origin of ffEV proteins. The limited abundance of several mRNAs within follicular cells indicated that corresponding ffEV proteins likely originated from circulating exosomes released by other tissues. Analysis of bovine ffEV transcriptome revealed that mRNAs present in ffEV accounted for only 18.3% of detected ffEV proteins. In conclusion, our study revealed numerous proteins within ffEVs, which originated from follicular and other cells. These proteins are likely involved in the maintenance of follicular homeostasis and may affect oocyte competence.

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S100‐A9 protein in exosomes derived from follicular fluid promotes inflammation via activation of NF‐κB pathway in polycystic ovary syndrome

Cited by 75 publications

References 59 publications

Identification of Milk Fat Metabolism-Related Pathways of the Bovine Mammary Gland during Mid and Late Lactation and Functional Verification of the ACSL4 Gene

Identification of Milk Fat Metabolism-Related Pathways of the Bovine Mammary Gland during Mid and Late Lactation and Functional Verification of the ACSL4 Gene

Extracellular Vesicles: Recent Developments in Aging and Reproductive Diseases

Protein Cargo of Extracellular Vesicles From Bovine Follicular Fluid and Analysis of Their Origin From Different Ovarian Cells

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