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Exosomes liver

Li Chen, David R Brigstock
Liver fibrosis occurs during chronic injury and represents, in large part, an exaggerated matrigenic output by hepatic stellate cells (HSCs) which become activated as a result of injury-induced signaling pathways in parenchymal and inflammatory cells (hepatocytes, macrophages, etc.). The molecular components in these pathways (e.g., CCN proteins) are modulated by transcription factors as well as by factors such as microRNAs (miRs) that act posttranscriptionally. MiRs are small (~23 nt) noncoding RNAs that regulate gene expression by specifically interacting with the 3' untranslated region (UTR) of target gene mRNA to repress translation or enhance mRNA cleavage...
2017: Methods in Molecular Biology
Chonlada Charoenviriyakul, Yuki Takahashi, Masaki Morishita, Akihiro Matsumoto, Makiya Nishikawa, Yoshinobu Takakura
Exosomes are small membrane vesicles secreted from cells and are expected to be used as drug delivery systems. Important characteristics of exosomes, such as yield, physicochemical properties, and pharmacokinetics, may be different among different cell types. However, there is limited information about the effect of cell type on these characteristics. In the present study, we evaluated these characteristics of exosomes derived from five different types of mouse cell lines: B16BL6 murine melanoma cells, C2C12 murine myoblast cells, NIH3T3 murine fibroblasts cells, MAEC murine aortic endothelial cells, and RAW264...
October 5, 2016: European Journal of Pharmaceutical Sciences
Zhen Qu, Junhua Wu, Junyi Wu, Dongjun Luo, Chunping Jiang, Yitao Ding
BACKGROUND: Exosomes are carriers of intercellular information and regulate the tumor microenvironment. They play an important role in drug resistance by transporting RNA molecules and proteins. However, their effects on sorafenib resistance in hepatocellular carcinoma (HCC) are not completely understood. METHODS: Exosomes were isolated from two invasive hepatoma cell lines (MHCC-97 L and MHCC-97H), and their roles in regulating sorafenib resistance in liver cancer cells as well as the underlying molecular mechanisms were determined...
September 30, 2016: Journal of Experimental & Clinical Cancer Research: CR
Naibin Yang, Shanshan Li, Guoxiang Li, Shengguo Zhang, Xinyue Tang, Shunlan Ni, Xiaomin Jian, Cunlai Xu, Jiayin Zhu, Mingqin Lu
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC...
October 4, 2016: Oncotarget
Tomoyuki Yuasa, Kikuko Amo-Shiinoki, Shuhei Ishikura, Mitsuyoshi Takahara, Takaaki Matsuoka, Hideaki Kaneto, Akio Kuroda, Munehide Matsuhisa, Seiichi Hashida
AIMS/HYPOTHESIS: Soluble insulin receptor (sIR), the ectodomain of the insulin receptor (IR), has been detected in human plasma and its concentration paralleled that of blood glucose. We have previously developed an in vitro model using HepG2 liver-derived cells, which mimics changes in sIR levels in plasma from diabetic patients and shows that calcium-dependent proteases cleave IR extracellularly (a process known as shedding). The present study aimed to reveal the mechanisms of IR cleavage...
September 30, 2016: Diabetologia
Silvio Holzner, Daniel Senfter, Serena Stadler, Anna Staribacher, Chi Huu Nguyen, Anna Gaggl, Silvana Geleff, Nicole Huttary, Sigurd Krieger, Walter Jäger, Helmut Dolznig, Robert M Mader, Georg Krupitza
Since cancer cells, when grown as spheroids, display drug sensitivity and radiation resistance patterns such as seen in vivo we recently established a three‑dimensional (3D) in vitro model recapitulating colorectal cancer (CRC)-triggered lymphatic endothelial cell (LEC)‑barrier breaching to study mechanisms of intra‑/extravasation. CRC metastasizes not only through lymphatics but also through blood vessels and here we extend the 3D model to the interaction of blood endothelial cells (BECs) with naïve and 5‑fluorouracil (5‑FU)‑resistant CRC CCL227 cells...
September 20, 2016: Oncology Reports
Li Chen, Ruju Chen, Victoria M Velazquez, David R Brigstock
Pathways of liver fibrosis are controlled by connective tissue growth factor (CCN2). In this study, CCN2 was identified as a target of miR-199a-5p, which was principally expressed in quiescent mouse hepatic stellate cells (HSCs) and directly suppressed production of CCN2. Up-regulated CCN2 expression in fibrotic mouse livers or in activated primary mouse HSCs was associated with miR-199a-5p down-regulation. MiR-199a-5p in quiescent mouse HSCs inhibited the activity of a wild-type CCN2 3' untranslated region (3'-UTR) but not of a mutant CCN2 3'-UTR lacking the miR-199a-5p-binding site...
September 20, 2016: American Journal of Pathology
Akihiro Matsumoto, Yuki Takahashi, Makiya Nishikawa, Kohei Sano, Masaki Morishita, Chonlada Charoenviriyakul, Hideo Saji, Yoshinobu Takakura
Exosomes are cell-derived extracellular vesicles that function as intercellular delivery carriers. Our previous study demonstrated that macrophages in the liver contributed to the rapid clearance of intravenously administered B16BL6-derived exosomes from the systemic circulation in mice. Phosphatidylserine (PS) may be responsible for this clearance because it is exposed on the surface of exosomes and is recognized by macrophages. In this study, the role of PS exposed on the membranes of exosomes in the uptake of B16BL6-derived exosomes by macrophages was investigated...
September 17, 2016: Journal of Pharmaceutical Sciences
Ben Ma, Jing-Yue Yang, Wen-Jie Song, Rui Ding, Zhuo-Chao Zhang, Hong-Chen Ji, Xuan Zhang, Jian-Lin Wang, Xi-Sheng Yang, Kai-Shan Tao, Ke-Feng Dou, Xiao Li
Allograft tolerance is the ultimate goal in the field of transplantation immunology. Immature dendritic cells (imDCs) play an important role in establishing tolerance but have limitations, including potential for maturation, short lifespan in vivo and short storage times in vitro. However, exosomes (generally 30-100 nm) from imDCs (imDex) retain many source cell properties and may overcome these limitations. In previous reports, imDex prolonged the survival time of heart or intestine allografts. However, tolerance or long-term survival was not achieved unless immune suppressants were used...
2016: Scientific Reports
Helena A Yu, Leslie Perez, Qing Chang, Sizhi P Gao, Mark G Kris, Gregory J Riely, Jacqueline Bromberg
INTRODUCTION: Resistance to EGFR tyrosine kinase inhibitors develops in patients with EGFR-mutant lung cancers. New treatments are needed to address resistance not mediated by EGFR T790M; preclinical evidence suggests that the Janus kinase/signal transducers and activators of transcription signaling pathway is important in acquired resistance to EGFR-directed therapy. METHODS: We evaluated the toxicity and efficacy of erlotinib and ruxolitinib in patients with EGFR-mutant lung cancers with acquired resistance to erlotinib...
September 6, 2016: Journal of Thoracic Oncology
Yu Zhou, Xu Wang, Li Sun, Li Zhou, Tong-Cui Ma, Li Song, Jian-Guo Wu, Jie-Liang Li, Wen-Zhe Ho
Exosomes are a class of cell-released small vesicles that mediate intercellular communication by delivering functional factors to recipient cells. During hepatitis C virus (HCV) infection, the interaction between liver resident macrophages and hepatocytes is a key component in liver innate immunity. In this study, we explored the role of exosomes in the delivery of innate anti-HCV factors to hepatocytes from macrophages. We showed that supernatant from TLR3-activated macrophage cultures could efficiently inhibit HCV replication in Huh7 cells...
September 7, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Wanbo Liu, Sheng Chen, Bing Liu
BACKGROUND: Hepatoblastoma (HB) is the most common primary malignant tumor of the liver in young children. The aim of this study is to identify the diagnostic and prognostic values of serum exosomal miR-21 in Chinese patients with HB. METHODS: We retrospectively reviewed 32 children with HB. The expressions of miR-21 were detected by real-time PCR. The comparison of diagnostic performance of plasmatic, exosomal miR-21 and AFP levels was measured using the Area Under ROC Curve...
November 2016: Pediatric Surgery International
Kate Nong, Weiwei Wang, Xin Niu, Bin Hu, Chenchao Ma, Yueqing Bai, Bo Wu, Yang Wang, Kaixing Ai
BACKGROUND: This study aimed to evaluate the effect of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo) on hepatic ischemia-reperfusion (I/R) injury. METHODS: Exosomes were isolated and concentrated from conditioned medium using ultracentrifugation and ultrafiltration. hiPSC-MSCs-Exo were injected systemically via the inferior vena cava in a rat model of 70% warm hepatic I/R injury, and the therapeutic effect was evaluated...
August 31, 2016: Cytotherapy
Hiroyuki Nojima, Takanori Konishi, Christopher M Freeman, Rebecca M Schuster, Lukasz Japtok, Burkhard Kleuser, Michael J Edwards, Erich Gulbins, Alex B Lentsch
Exosomes are small membrane vesicles released by different cell types, including hepatocytes, that play important roles in intercellular communication. We have previously demonstrated that hepatocyte-derived exosomes contain the synthetic machinery to form sphingosine-1-phosphate (S1P) in target hepatocytes resulting in proliferation and liver regeneration after ischemia/reperfusion (I/R) injury. We also demonstrated that the chemokine receptors, CXCR1 and CXCR2, regulate liver recovery and regeneration after I/R injury...
2016: PloS One
Shuangpeng Cai, Xiaoyu Cheng, Xueyin Pan, Jun Li
Exosomes can meditate intercellular communication by conveying various bioactive molecules. Plentiful evidences suggest that exosomes are involved in many liver diseases including hepatitis C virus(HCV) infection, hepatitis B virus(HBV) infection, hepatocellualr carcinoma(HCC), liver fibrosis, cirrhosis, non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD). Moreover, exosomes are presented in nearly all human body fluids. Therefore, exosomal miRNA or proteins have the potential to be the novel biomarkers of liver diseases...
August 18, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Keisaku Sato, Fanyin Meng, Shannon Glaser, Gianfranco Alpini
No abstract text is available yet for this article.
September 2016: Journal of Hepatology
Dionysios C Watson, Defne Bayik, Avinash Srivatsan, Cristina Bergamaschi, Antonio Valentin, Gang Niu, Jenifer Bear, Mitchell Monninger, Mei Sun, Aizea Morales-Kastresana, Jennifer C Jones, Barbara K Felber, Xiaoyuan Chen, Ihsan Gursel, George N Pavlakis
Extracellular vesicles (EV), including exosomes and microvesicles, are nano-sized intercellular communication vehicles that participate in a multitude of physiological processes. Due to their biological properties, they are also promising candidates for the systemic delivery of therapeutic compounds, such as cytokines, chemotherapeutic drugs, siRNAs and viral vectors. However, low EV production yield and rapid clearance of administered EV by liver macrophages limit their potential use as therapeutic vehicles...
October 2016: Biomaterials
Shilpa Kulkarni, Antonius Koller, Kartik M Mani, Ruofeng Wen, Alan Alfieri, Subhrajit Saha, Jian Wang, Purvi Patel, Nuno Bandeira, Chandan Guha, Emily I Chen
PURPOSE: Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis. Recent research has also suggested that exosomes are a reliable source of biomarkers in disease progression. In the present study, we analyzed total urine proteome and exosomes isolated from urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI)...
November 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Laia Bonjoch, Vanessa Casas, Montserrat Carrascal, Daniel Closa
A frequent complication of acute pancreatitis is the lung damage associated with the systemic inflammatory response. Although various pro-inflammatory mediators generated at both local and systemic levels have been identified, the pathogenic mechanisms of the disease are still poorly understood. In recent years, exosomes have emerged as a new intercellular communication system able to transfer encapsulated proteins and small RNAs and protect them from degradation. Using an experimental model of taurocholate-induced acute pancreatitis in rats, we aimed to evaluate the role of exosomes in the extent of the systemic inflammatory response...
October 2016: Journal of Pathology
Martina Angi, Helen Kalirai, Samuel Prendergast, Deborah Simpson, Dean E Hammond, Michele C Madigan, Robert J Beynon, Sarah E Coupland
Uveal melanoma (UM), the most common primary intraocular tumour in adults, is characterised by a high frequency of metastases to the liver, typically with a fatal outcome. Proteins secreted from cancer cells ('secretome') are biologically important molecules thought to contribute to tumour progression. We examined the UM secretome by applying a label-free nanoLCMS/MS proteomic approach to profile proteins secreted into culture media by primary UM tumours with a high- (HR; n = 11) or low- (LR; n = 4) metastatic risk, compared to normal choroidal melanocytes (NCM) from unaffected post-mortem eyes...
July 6, 2016: Oncotarget
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