Abstract:
:Hepatocyte exosomes (ExoHep) are proposed to mediate physiological or pathophysiological signaling in a variety of hepatic target cells. ExoHep were purified from the medium of primary mouse hepatocytes or AML12 cells and characterized as ~100 nm nanovesicles that were positive for proteins commonly found in exosomes (CD9, CD81, flotillin) or hepatocytes (asialoglycoprotein receptor). Ethanol treatment of hepatocytes caused increased ExoHep release and increased cellular mRNA expression of components involved in intracellular vesicle trafficking (Rab 5a,b,c, Rab 7a, Rab 27a,b) or exosome biogenesis via the ESCRT (HGS, Alix, STAM1, TSG101, VTA1, YKT6) or ceramide (nSmase2) pathways. RNA interference of HGS, Alix, TSG101 or nSmase 2 caused exosome production by normal or ethanol-treated hepatocytes to be reduced. In mice, in vivo administration of fluorescently-labeled ExoHep resulted in their accumulation in the liver and preferential localization to hepatic stellate cells (HSC) or hepatocytes, the latter of which showed enhanced ExoHep binding when isolated from fibrotic mice. In cell co-cultures, the intercellular transfer of RNA from hepatocytes to hepatocytes or HSC was blocked by the exosome inhibitor GW4869. ExoHep binding to HSC or hepatocytes occurred via mechanisms that involved heparin-like molecules and cellular integrin αv or β1 subunits , and resulted in a reversal of fibrosis-associated gene expression in HSC and of ethanol-induced damage in hepatocytes. These studies provide insight regarding the regulation and/or participation of exosome biogenesis or trafficking components in hepatocytes and show that ExoHep can mediate therapeutic changes in activated HSC or injured hepatocytes that occur downstream of heparin- or integrin-dependent binding interactions.
journal_name
J Cell Commun Signaljournal_title
Journal of cell communication and signalingauthors
Chen L,Chen R,Kemper S,Brigstock DRdoi
10.1007/s12079-017-0421-7subject
Has Abstractpub_date
2018-03-01 00:00:00pages
343-357issue
1eissn
1873-9601issn
1873-961Xpii
10.1007/s12079-017-0421-7journal_volume
12pub_type
杂志文章abstract::Thrombopoietin (THPO), also known as megakaryocyte growth and development factor (MGDF), is a cytokine involved in the production of platelets. THPO is a glycoprotein produced by liver and kidney. It regulates the production of platelets by stimulating the differentiation and maturation of megakaryocyte progenitors. I...
journal_title:Journal of cell communication and signaling
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journal_title:Journal of cell communication and signaling
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journal_title:Journal of cell communication and signaling
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journal_title:Journal of cell communication and signaling
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doi:10.1007/s12079-020-00546-7
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journal_title:Journal of cell communication and signaling
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journal_title:Journal of cell communication and signaling
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journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-018-0490-2
更新日期:2019-06-01 00:00:00
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journal_title:Journal of cell communication and signaling
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更新日期:2019-09-01 00:00:00
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journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-014-0251-9
更新日期:2014-12-01 00:00:00
abstract::Because of differences in the downstream signaling patterns of its pathways, the role of the human epidermal growth factor family of receptors (HER) in promoting cell growth and survival is cell line and context dependent. Using two model cell lines, we have studied how the regulatory interaction network among the key...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-017-0389-3
更新日期:2017-12-01 00:00:00
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journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-011-0156-9
更新日期:2012-03-01 00:00:00
abstract::The ubiquitin proteasome pathway plays a critical role in regulating many processes in the cell which are important for tumour cell growth and survival. Inhibition of proteasome function has emerged as a powerful strategy for anti-cancer therapy. Clinical validation of the proteasome as a therapeutic target was achiev...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-011-0121-7
更新日期:2011-06-01 00:00:00
abstract::Fibrotic diseases are a significant cause of mortality. It is being increasingly appreciated that the cellular microenvironment plays a key role in promoting pathological fibrosis. A previous Bits and Bytes described an elegant series of experiments published by Bruce Riser and colleagues (Am J Pathol. 2009: 174:1725-...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-015-0281-y
更新日期:2015-03-01 00:00:00
abstract::The Fifth International Workshop on the CCN Family of Genes was held in Toronto October 18-22, 2008. This bi-annual workshop provides a unique opportunity for the presentation and discussion of cutting edge research in the CCN field. The CCN family members have emerged as extracellular matrix associated proteins which...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-009-0036-8
更新日期:2008-12-01 00:00:00
abstract::CCN3 is a member of the CCN family of cell growth and differentiation regulators that play key roles during embryonic development, and are associated with severe human pathologies. The level of CCN genes' expression is of prognostic value in several types of tumors. In the present manuscript, we report the isolation a...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-007-0009-8
更新日期:2007-09-01 00:00:00
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journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-012-0183-1
更新日期:2013-03-01 00:00:00
abstract::The activity of the Insulin-like Growth Factors (IGFs) ligands elicited via their receptors and transduced by various intracellular signal pathways is modulated by the IGF Binding Proteins (IGFBPs). Among all the IGFBPs, IGFBP-2 has been implicated in the regulation of IGF activity in most tissue and organs. Besides b...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-015-0261-2
更新日期:2015-06-01 00:00:00
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journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-008-0018-2
更新日期:2007-12-01 00:00:00
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journal_title:Journal of cell communication and signaling
pub_type: 杂志文章,评审
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abstract::The CCN family of proteins consists of six members with conserved structural features. These proteins play several roles in the physiology and pathology of cells. Among the pathological roles of the CCN family, one of the most important and controversial ones is their role in the expansion and metastasis of cancer. Up...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-011-0133-3
更新日期:2011-12-01 00:00:00
abstract::Extracellular molecules coordinate the multiple signaling pathways spatiotemporally to exchange information between cells during development. Understanding the regulation of these signal molecule-dependent pathways elucidates the mechanism of intercellular crosstalks. CCN2/CTGF is one of the CCN family members that bi...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-018-0487-x
更新日期:2019-03-01 00:00:00
abstract::It is well-established that the expression of CCN family of matricellular proteins is altered in essentially all cancers and, hence, targeting these proteins may be a novel therapeutic approach to treating these diseases. For example, CCN6 (WISP3) is downregulated in aggressive breast cancers, and this phenomenon appe...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-012-0189-8
更新日期:2013-06-01 00:00:00
abstract::We have recently identified several novel ATP-independent inhibitors that target the extracellular signal-regulated kinase-2 (ERK2) protein and inhibit substrate phosphorylation. To further characterize these compounds, we describe the use of C. elegans as a model organism. C. elegans is recognized as a versatile and ...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-008-0034-2
更新日期:2008-12-01 00:00:00
abstract::The discovery of the gap junction structure, its functions and the family of the "connexin" genes, has been basically ignored by the major biological disciplines. These connexin genes code for proteins that organize to form membrane-associated hemi-channels, "connexons", co-join with the connexons of neighboring cells...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-010-0108-9
更新日期:2011-03-01 00:00:00
abstract::The Kallikrein Kinin System (KKS) is a vasoactive peptide system with known functions in the maintenance of tissue homeostasis, renal function and blood pressure. The main effector peptide of KKS is Bradykinin (BK). This ligand has two receptors: a constitutive B2 receptor (B2R), which has been suggested to have anti-...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-017-0439-x
更新日期:2018-09-01 00:00:00
abstract::Glutamine (gln) metabolism has emerged as a cancer therapeutic target in past few years, however, the effect of gln-deprivation of bCSCs remains elusive in breast cancer. In this study, effect of glutamine on stemness and differentiation potential of bCSCs isolated from MCF-7 and MDAMB-231 were studied. We have shown ...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-020-00603-1
更新日期:2021-01-28 00:00:00
abstract::The lectin from Canavalia ensiformis (Concanavalin-A, ConA), one of the most abundant lectins known, enables one to mimic biological lectin/carbohydrate interactions that regulate extracellular matrix protein recognition. As such, ConA is known to induce membrane type-1 matrix metalloproteinase (MT1-MMP) which express...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-009-0084-0
更新日期:2010-03-01 00:00:00
abstract::Hepatoblastoma (HB) is one of the most common liver malignancies in children, while the molecular basis of the disease is largely unknown. Therefore, this study aims to explore the key genes and molecular mechanisms of the pathogenesis of HB using a bioinformatics approach. The gene expression dataset GSE131329 was us...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-020-00584-1
更新日期:2020-10-13 00:00:00
abstract::Mice lacking the pro-adhesive matricellular protein connective tissue growth factor (CTGF/CCN2) display an embryonic lethal phenotype due to defects in bone and cartilage. However, the specific role of CCN2 in skin development is unknown. Here, we generated mice deleted for CCN2 in the entire body (using a cre/lox sys...
journal_title:Journal of cell communication and signaling
pub_type: 杂志文章
doi:10.1007/s12079-011-0129-z
更新日期:2011-08-01 00:00:00