Alpha-2-macroglobulin from circulating exosome-like vesicles is increased in women with preterm pregnancies

Tronco, Júlia Abbade; Ramos, Bruna Ribeiro de Andrade; Bastos, Natália Marins; Alcântara, Sérgio A; Silveira, Juliano Coelho da; Silva, Márcia G da

doi:10.1038/s41598-020-73772-z

Cited by 9 publications

(10 citation statements)

References 19 publications

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“…Several studies have reported the EV-mediated secretion of a2M ( 41 – 43 ). In western blot analysis, a2M was detected both in cell lysate and secreted EVs from BC cells ( Figure 6A ).…”

Section: Resultsmentioning

confidence: 99%

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Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles

et al. 2022

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Extracellular vesicles (EVs) derived from urine are promising tools for the diagnosis of urogenital cancers. Urinary EVs (uEVs) are considered potential biomarkers for bladder cancer (BC) because urine is in direct contact with the BC tumor microenvironment and thus reflects the current state of the disease. However, challenges associated with the effective isolation and analysis of uEVs complicate the clinical detection of uEV-associated protein biomarkers. Herein, we identified uEV-derived alpha-2-macroglobulin (a2M) as a novel diagnostic biomarker for BC through comparative analysis of uEVs obtained from patients with BC pre- and post-operation using an antibody array. Furthermore, enzyme-linked immunosorbent assay of uEVs isolated from patients with BC (n=60) and non-cancer control subjects (n=23) validated the significant upregulation of a2M expression in patient uEVs (p<0.0001). There was no significant difference in whole urine a2M levels between patients with BC and controls (p=0.317). We observed that compared to classical differential centrifugation, ExoDisc, a centrifugal microfluidic tangential flow filtration device, was a significantly more effective separation method for uEV protein analysis. We expect that our approach for EV analysis will provide an efficient route for the identification of clinically meaningful uEV-based biomarkers for cancer diagnosis.

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“…Several studies have reported the EV-mediated secretion of a2M ( 41 – 43 ). In western blot analysis, a2M was detected both in cell lysate and secreted EVs from BC cells ( Figure 6A ).…”

Section: Resultsmentioning

confidence: 99%

“…Several studies have reported the EV-mediated secretion of a2M (41)(42)(43). In western blot analysis, a2M was detected both 6A).…”

Section: A2m From Bc Is Co-fractionated With Common Ev Markersmentioning

confidence: 94%

Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles

et al. 2022

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“…Western blot was performed to detect the exosome marker CD63; the negative control was cytochrome c (Santa Cruz Biotechnology, Inc.—Texas, USA). This step was performed jointly with another study from our group that has already been published [ 52 ]. Briefly, 4× Laemmli buffer and mercaptoethanol (1:10) were used for protein extraction (5 min at 95 °C).…”

Section: Methodsmentioning

confidence: 99%

Circulating Extracellular Vesicles microRNAs Are Altered in Women Undergoing Preterm Birth

Ramos

Tronco

Carvalho

et al. 2023

IJMS

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Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to high perinatal morbidity/mortality rates worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that may contribute to the pathogenesis of these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies. This cross-sectional study included women who underwent PTL, PPROM, and term pregnancies, examined at the Botucatu Medical School Hospital, SP, Brazil. sEV were isolated from plasma. Western blot used to detect exosomal protein CD63 and nanoparticle tracking analysis were performed. The expression of 800 miRNAs was assessed by the nCounter Humanv3 miRNA Assay (NanoString). The miRNA expression and relative risk were determined. Samples from 31 women—15 preterm and 16 term—were included. miR-612 expression was increased in the preterm groups. miR-612 has been shown to increase apoptosis in tumor cells and to regulate the nuclear factor κB inflammatory pathway, processes involved in PTL/PPROM pathogenesis. miR-1253, miR-1283, miR378e, and miR-579-3p, all associated with cellular senescence, were downregulated in PPROM compared with term pregnancies. We conclude that miRNAs from circulating sEV are differentially expressed between term and preterm pregnancies and modulate genes in pathways that are relevant to PTL/PPROM pathogenesis.

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“…Moreover, we measured the particle sizes of PMSC-Exos with nanoparticle tracking analysis (NTA) using ZetaView PMX 110 (Particle Metrix) and its corresponding software ZetaView 8.04.02. PMSC-Exos were diluted in sterile PBS before NTA analysis [ 26 ]. NTA measurement was recorded and analyzed at 11 positions.…”

Section: Methodsmentioning

confidence: 99%

Exosomes derived from human placental mesenchymal stem cells ameliorate myocardial infarction via anti-inflammation and restoring gut dysbiosis

Yang

Wang

Zhang

et al. 2022

BMC Cardiovasc Disord

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Background Myocardial infarction (MI) represents a severe cardiovascular disease with limited therapeutic agents. This study was aimed to elucidate the role of the exosomes derived from human placental mesenchymal stem cells (PMSCs-Exos) in MI. Methods PMSCs were isolated and cultured in vitro, with identification by both transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). To further investigate the effects of PMSC-Exos on MI, C57BL/6 mice were randomly divided into Sham group, MI group, and PMSC-Exos group. After 4 weeks of the intervention, cardiac function was assessed by cardiac echocardiography, electrocardiogram and masson trichrome staining; lipid indicators were determined by automatic biochemical instrument; inflammatory cytokines were measured by cytometric bead array (CBA); gut microbiota, microbial metabolites short chain fatty acids (SCFAs) as well as lipopolysaccharide (LPS) were separately investigated by 16S rRNA high throughput sequencing, gas chromatography mass spectrometry (GC–MS) and tachypleus amebocyte lysate kit; transcriptome analysis was used to test the transcriptional components (mRNA\miRNA\cirRNA\lncRNA) of PMSC-Exos. Results We found that human PMSC-Exos were obtained and identified with high purity and uniformity. MI model was successfully established. Compared to MI group, PMSC-Exos treatment ameliorated myocardial fibrosis and left ventricular (LV) remodeling (P < 0.05). Moreover, PMSC-Exos treatment obviously decreased MI molecular markers (AST/BNP/MYO/Tn-I/TC), pro-inflammatory indicators (IL-1β, IL-6, TNF-α, MCP-1), as well as increased HDL in comparison with MI group (all P < 0.05). Intriguingly, PMSC-Exos intervention notably modulated gut microbial community via increasing the relative abundances of Bacteroidetes, Proteobacteria, Verrucomicrobia, Actinobacteria, Akkermansia, Bacteroides, Bifidobacterium, Thauera and Ruminiclostridium, as well as decreasing Firmicutes (all P < 0.05), compared with MI group. Furthermore, PMSC-Exos supplementation increased gut microbiota metabolites SCFAs (butyric acid, isobutyric acid and valeric acid) and decreased LPS in comparison with MI group (all P < 0.05). Correlation analysis indicated close correlations among gut microbiota, microbial SCFAs and inflammation in MI. Conclusions Our study highlighted that PMSC-Exos intervention alleviated MI via modulating gut microbiota and suppressing inflammation.

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Alpha-2-macroglobulin from circulating exosome-like vesicles is increased in women with preterm pregnancies

Cited by 9 publications

References 19 publications

Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles

Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles

Circulating Extracellular Vesicles microRNAs Are Altered in Women Undergoing Preterm Birth

Exosomes derived from human placental mesenchymal stem cells ameliorate myocardial infarction via anti-inflammation and restoring gut dysbiosis

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