Exosomal Transfer of Vasorin Expressed in Hepatocellular Carcinoma Cells Promotes Migration of Human Umbilical Vein Endothelial Cells

Huang, Aixue; Dong, Jing; Li, Shaohua; Wang, Chaonan; Ding, Hongmei; Li, Hui; Su, Xueting; Ge, Xingfeng; Sun, Leqiao; Bai, Chenjun; Shen, Xuelian; Fang, Tao; Li, Jie; Shao, Ningsheng

doi:10.7150/ijbs.11943

Cited by 83 publications

(69 citation statements)

References 35 publications

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“…The second gene is Vasorin ( VASN ), which has three nonsynonymous mutations. This gene may be involved in modulating arterial response to injury by inhibiting the TGF- β signaling pathway222324. VASN is highly expressed in vascular smooth muscle cells (hence the name) and the developing skeletal system25.…”

Section: Resultsmentioning

confidence: 99%

Genomic analysis reveals selection in Chinese native black pig

Tang

et al. 2016

Sci Rep

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Identification of genomic signatures that help reveal mechanisms underlying desirable traits in domesticated pigs is of significant biological, agricultural and medical importance. To identify the genomic footprints left by selection during domestication of the Enshi black pig, a typical native and meat-lard breed in China, we generated about 72-fold coverage of the pig genome using pools of genomic DNA representing three different populations of Enshi black pigs from three different locations. Combining this data with the available whole genomes of 13 Chinese wild boars, we identified 417 protein-coding genes embedded in the selected regions of Enshi black pigs. These genes are mainly involved in developmental and metabolic processes, response to stimulus, and other biological processes. Signatures of selection were detected in genes involved in body size and immunity (RPS10 and VASN), lipid metabolism (GSK3), male fertility (INSL6) and developmental processes (TBX19). These findings provide a window into the potential genetic mechanism underlying development of desirable phenotypes in Enshi black pigs during domestication and subsequent artificial selection. Thus, our results illustrate how domestication has shaped patterns of genetic variation in Enshi black pigs and provide valuable genetic resources that enable effective use of pigs in agricultural production.

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Section: Resultsmentioning

confidence: 99%

Genomic analysis reveals selection in Chinese native black pig

Tang

et al. 2016

Sci Rep

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“…11e13 HepG2 hepatoblastoma cells were the first liver cell type for which exosome production was documented, 14 and recent reports have described exosomal pathways for a variety of hepatic cancer cells that result in delivery of RNAs or proteins and subsequent regulation of cancer cell proliferation, chemosensitivity or migration, 15e18 intercellular transmission of the hepatitis C virus, 19 or acquisition of a proangiogenic phenotype by endothelial cells. 20,21 However, a more expansive and highly complex role for exosomes in the liver is now emerging, with the recognition that a broad variety of hepatic cells, including hepatocytes, macrophages, cholangiocytes, and HSCs, produce exosomes that can influence a broad spectrum of cellular processes involved in liver repair after hepatectomy or pathogenesis associated with fibrosis, alcoholic liver disease, nonalcoholic steatohepatitis, or nonalcoholic fatty liver disease. 10,22e31 A question of particular interest is whether quiescent HSCs produce exosomes that contain a cargo that has the ability to attenuate the function of activated HSCs.…”

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confidence: 99%

Fibrogenic Signaling Is Suppressed in Hepatic Stellate Cells through Targeting of Connective Tissue Growth Factor (CCN2) by Cellular or Exosomal MicroRNA-199a-5p

Chen

Velazquez

et al. 2016

The American Journal of Pathology

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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 downregulation. MiR-199a-5p in quiescent mouse HSCs inhibited the activity of a wild-type CCN2 3 0 untranslated region (3 0 -UTR) but not of a mutant CCN2 3 0 -UTR lacking the miR-199a-5p-binding site. In activated mouse HSCs, CCN2, a-smooth muscle actin, and collagen 1(a1) were suppressed by a miR199a-5p mimic, whereas in quiescent mouse HSCs, the inhibited CCN2 3 0 -UTR activity was blocked by a miR-199a-5p antagomir. CCN2 3 0 -UTR activity in human HSCs was reduced by a miR-199a-5p mimic. MiR-199a-5p was present at higher levels in exosomes from quiescent versus activated HSCs. MiR-199a-5pecontaining exosomes were shuttled from quiescent mouse HSCs to activated mouse HSCs in which CCN2 3 0 -UTR activity was then suppressed. Exosomes from quiescent HSCs caused miR-199a-5pe dependent inhibition of CCN2, a-smooth muscle actin, or collagen 1(a1) in activated HSCs in vitro and bound to activated HSCs in vivo. Thus, CCN2 suppression by miR-199a-5p accounts, in part, for lowlevel fibrogenic gene expression in quiescent HSCs and causes dampened gene expression in activated HSCs after horizontal transfer of miR-199a-5p in exosomes from quiescent HSCs. (Am J Pathol 2016, 186: 2921e2933; http://dx

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“…HepG2-derived exosomes contain vasorin, which can enhance the migration of human umbilical vein endothelial cells (HUVECs) (64). CD90+ liver cancer cells (known 6 Hepat Mon.…”

Section: The Role Of Exosomes In Tumorigenesis and The Development Ofmentioning

confidence: 99%

Exosome: An Emerging Participant in the Development of Liver Disease

Guo

Wang

et al. 2017

Hepat Mon

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Context: An exosome is a type of extracellular vesicle with a diameter of 30 -100 nm and a density of 1.13 -1.19 g/m. Exosomes exist in almost all body fluids and can be secreted and absorbed by most cells. They deliver information and molecules that participate in intracellular communication, thus contributing to the progression of various diseases, such as liver diseases. Evidence Acquisition: In this study we collected and summarized the most important and new data available on the role of exosome in liver diseases by the PubMed search. The study data were collected through searching the related keywords then classified and summarized. Results: In this review, we summarize the research findings regarding the roles of exosomes in liver physiology and pathology, mainly focusing on liver diseases such as viral hepatitis, liver cancer (mostly hepatocellular carcinoma [HCC]), and liver injury caused by other pathogenic factors (alcohol, drugs, hepatotoxins, high-fat diets, parasites, etc.). Conclusions: These studies revealed the involvement of exosomes in various aspects of liver physiology and pathology and in the progress of liver diseases. More importantly, it offers a promising new direction for disease diagnosis and treatment.

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Exosomal Transfer of Vasorin Expressed in Hepatocellular Carcinoma Cells Promotes Migration of Human Umbilical Vein Endothelial Cells

Cited by 83 publications

References 35 publications

Genomic analysis reveals selection in Chinese native black pig

Genomic analysis reveals selection in Chinese native black pig

Fibrogenic Signaling Is Suppressed in Hepatic Stellate Cells through Targeting of Connective Tissue Growth Factor (CCN2) by Cellular or Exosomal MicroRNA-199a-5p

Exosome: An Emerging Participant in the Development of Liver Disease

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