Exosomes from high glucose-treated glomerular endothelial cells trigger the epithelial-mesenchymal transition and dysfunction of podocytes

Scientific Reports, Journal Year: 2017, Volume and Issue: 7(1)

Published: Aug. 18, 2017

New data indicate that abnormal glomerular endothelial cell (GEC)-podocyte crosstalk plays a critical role in diabetic nephropathy (DN). The aim of our study is to investigate the exosomes from high glucose (HG)-treated GECs epithelial-mesenchymal transition (EMT) and dysfunction podocytes. In this study, were extracted GEC culture supernatants podocytes incubated with GEC-derived exosomes. Here, we demonstrate HG induces endothelial-mesenchymal (EndoMT) HG-treated cells undergoing EndoMT secrete more than normal (NG)-treated GECs. We show can be internalized by an EndoMT-like process trigger podocyte EMT barrier dysfunction. Our reveals TGF-β1 mRNA enriched probably mediates addition, experimental results illustrate canonical Wnt/β-catenin signaling involved exosome-induced EMT. findings suggest importance paracrine communication via between for renal fibrosis DN. Thus, protecting inhibiting TGF-β1-containing release necessary manage

Language: Английский

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Extracellular vesicles swarm the cancer microenvironment: from tumor–stroma communication to drug intervention

Oncogene, Journal Year: 2016, Volume and Issue: 36(7), P. 877 - 884

Published: Aug. 22, 2016

Language: Английский

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Neural stem cell-derived exosomes facilitate spinal cord functional recovery after injury by promoting angiogenesis

Experimental Biology and Medicine, Journal Year: 2020, Volume and Issue: 245(1), P. 54 - 65

Published: Jan. 1, 2020

Acute traumatic spinal cord injury is a devastating event without effective therapeutic approach. The feeble plasticity of microvascular endothelial cells (SCMECs) after trauma one the major causes for exacerbation injury. Therefore, improving and regeneration SCMECs crucial to promote recovery For present study, we explored influence exosomes derived from neural stem (NSCs-Exos) on determined underlying mechanisms. After primary NSCs were extracted, isolated conditioned medium used co-incubated with in vitro, then effect angiogenic activities was measured. candidate molecules involved NSCs-Exos-mediated angiogenesis screened using Western blotting. NSCs-Exos functional vivo analyzed. results demonstrated that could enhance SCMECs, highly enriched VEGF-A. level VEGF-A downregulated shVEGF-A -Exos pro-angiogenic effects cocultured inhibited. Furthermore, significantly accelerated regeneration, reduced cavity, improved Basso mouse scale scores mice. This work provides evidence mechanism suggests novel target Impact statement SCI. ability Our current study uncovered migration, tube formation proliferation further identified exosomal mediated effect. observed remarkable density increase, cavity shrinkage, motor function SCI mice treated NSCs-Exos, which confirmed alleviate Downregulating partially abolished these NSCs-Exos. first reveal has by transferring tissue healing, indicating can become promising bioagent facilitating

Language: Английский

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Role of stem cell derived exosomes in tumor biology

International Journal of Cancer, Journal Year: 2017, Volume and Issue: 142(6), P. 1086 - 1092

Published: Oct. 6, 2017

Exosomes are nano-scale messengers loaded with bio-molecular cargo of RNA, DNA, and Proteins. As a master regulator cellular signaling, stem cell (both normal, cancer cells) secreted exosome orchestrate various autocrine paracrine functions which alter tumor micro-environment, growth progression. by one the two important phenotypes in cancers a) Mesenchymal cells, b) Cancer cells not only promote cancerous but also impart therapy resistance cells. In tumors, normal or mesenchymal (MSCs) derived exosomes (MSC-exo) modulate hallmarks delivering unique miRNA species to neighboring help Apart from regulating fate, MSC-exo capable inducing physiological processes, for example, angiogenesis, metastasis so forth. Similarly, (CSCs) (CSC-exo) contain stemness-specific proteins, self-renewal promoting regulatory miRNAs, survival factors. CSC-exo specific maintains heterogeneity alters this review we critically discuss importance signaling pathways their role biology.

Language: Английский

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Extracellular Vesicles in Glioblastoma Tumor Microenvironment

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 10

Published: Jan. 21, 2020

Glioblastomas (GBM) are highly aggressive primary brain tumors. Complex and dynamic tumor microenvironment (TME) plays a crucial role in the sustained growth, proliferation, ​and invasion of GBM. Several means intercellular communication have been documented between glioma cells TME, including growth factors, cytokines, chemokines as well extracellular vesicles (EVs). EVs carry functional genomic proteomic cargo from their parental deliver that information to surrounding distant recipient modulate behavior. emerging mediators establishment maintenance by modulating TME into tumor-promoting system. Herein we review recent literature context GBM which reprogram metabolic activity, induce angiogenesis, escape immune surveillance, acquire drug resistance undergo invasion. Understanding multifaceted roles niche will provide invaluable insights understanding biology EV-mediated during gliomagenesis.

Language: Английский

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Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p

Thorax, Journal Year: 2020, Volume and Issue: 75(10), P. 870 - 881

Published: Aug. 5, 2020

Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported dysregulation exosomal microRNAs (miRs) in the IPF context. However, impact IPF-related miRs on progression unknown. Methods Two independent cohorts were enrolled at ambulatory care polyclinic Liège University. Exosomes from sputum obtained 19 patients with 23 healthy subjects (HSs) (cohort 1), ones plasma derived 14 HSs 2). Exosomal miR expression was performed by quantitative reverse transcription–PCR. The functional role assessed vitro transfecting mimics human alveolar epithelial cells fibroblasts. Results analysis showed that miR-142-3p significantly upregulated (8.06-fold, p<0.0001; 1.64 fold, p=0.008, respectively). Correlation revealed positive association between percentage macrophages (r=0.576, p=0.012), suggesting macrophage origin upregulation. overexpression fibroblasts able to reduce transforming growth factor β receptor 1 (TGFβ-R1) profibrotic genes. Furthermore, exosomes isolated present antifibrotic properties due part repression TGFβ-R1 transfer target cells. Discussion Our results suggest macrophage-derived may fight against via delivery miR-142–3 p

Language: Английский

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MiR-454-3p-Mediated Wnt/β-catenin Signaling Antagonists Suppression Promotes Breast Cancer Metastasis

Theranostics, Journal Year: 2019, Volume and Issue: 9(2), P. 449 - 465

Published: Jan. 1, 2019

The Wnt/β-catenin pathway is constitutively active and promotes multiple tumor processes, including breast cancer metastasis. However, the underlying mechanism by which activated in metastasis remains unclear. Inhibition of Wnt antagonists important for signaling activation, post-transcriptional regulation these microRNAs (miRNAs) might be a possible activation. Regulation nuclear pre-mRNA domain-containing 1A (RPRD1A) known inhibitor cell growth activity, but function regulatory RPRD1A have not been clarified. aim this study was to understand how regulators may play role cancer. Methods: expression its association with clinicopathological characteristics analyzed immunohistochemically human specimens. miR-454-3p using real-time PCR. or knockdown overexpression were used determine their functions cells. Xenografted model, 3D invasive culture, migration invasion assays sphere formation assay biofunction Electrophoretic mobility shift (EMSA), luciferase reporter assay, RNA immunoprecipitation (RIP) performed mechanisms correlation Results: antagonist downregulated upstream regulator amplified overexpressed metastatic cancer, both correlated overall relapse-free survival patients. suppression on found activate signaling, thereby promoting Simultaneously, three other negative pathway, namely, AXIN2, dickkopf WNT (DKK) 3 secreted frizzled related protein (SFRP) 1, also targets involved early processes promote stemness cells relapse under vitro vivo conditions. Conclusions: findings indicate that miR-454-3p-mediated RPRD1A, as well DKK3 SFRP1, sustains constitutive activation signaling; thus, potential diagnostic therapeutic

Language: Английский

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Exosomes from high glucose-treated glomerular endothelial cells activate mesangial cells to promote renal fibrosis

Biology Open, Journal Year: 2016, Volume and Issue: 5(4), P. 484 - 491

Published: March 23, 2016

The interaction between glomerular endothelial cells (GECs) and mesangial (GMCs) is an essential aspect of diabetic nephropathy (DN). Therefore, understanding how GECs communicate with GMCs in the environment crucial for development new targets prevention treatment DN. Exosomes, nanometer-sized extracellular membrane vesicles secreted by various cell types, play important roles cell-to-cell communication via transfer mRNA, microRNA protein. In this study, we demonstrate that high glucose (HG)-treated secrete a higher number exosomes highly enriched TGF-β1 mRNA compared normal (NG)-treated GECs. Exosomes released HG-treated can promote α-smooth muscle actin (α-SMA) expression, proliferation matrix protein overproduction through TGF-β1/Smad3 signaling pathway. Thus, provide insights into pathogenesis DN involves intercellular GEC-to-GMC direction exosomes.

Language: Английский

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Towards rationally designed biomanufacturing of therapeutic extracellular vesicles: impact of the bioproduction microenvironment

Biotechnology Advances, Journal Year: 2018, Volume and Issue: 36(8), P. 2051 - 2059

Published: Sept. 12, 2018

Language: Английский

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Endothelial Extracellular Vesicles—Promises and Challenges

Frontiers in Physiology, Journal Year: 2017, Volume and Issue: 8

Published: May 5, 2017

Extracellular vesicles, including exosomes, microparticles and apoptotic bodies, are phospholipid bilayer-enclosed vesicles that have once been considered as cell debris lacking biological functions. However, they recently gained immense interest in the scientific community due to their role intercellular communication, immunity, tissue regeneration well onset progression of various pathologic conditions. endothelial origin found play a versatile human body, since on one hand known contribute cardiovascular diseases, but other also reported promote survival. Hence, extracellular hold promising therapeutic potential be used new tool detect treat great number diseases. This calls for clinically approved, standardized, efficient isolation characterization protocols harvest purify vesicles. such methods techniques fulfill stringent requirements clinical trials yet developed or not harmonized internationally. In this review, recent advances challenges field vesicle research discussed current problems limitations regarding pointed out.

Language: Английский

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