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| Status |
Public on Aug 05, 2009 |
| Title |
Human liver stem cells-derived microvesicles accelerate hepatic regeneration in partially hepatectomized rats |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Several studies indicate that adult stem cells may improve the recovery from acute tissue injury. It has been suggested that they may contribute to tissue regeneration by the release of paracrine factors promoting proliferation of tissue resident cells. However, the factors involved remain unknown. In the present study we found that microvesicles (MV) derived from human liver stem cells (HLSC) were able to stimulate in vitro proliferation and apoptosis resistance of human and rat hepatocytes. These effects required internalization of MV in the hepatocytes by an alpha4 integrin-dependent mechanism. However, when treated with RNase, MV despites their internalization were unable to induce hepatocyte proliferation and apoptosis resistance, suggesting an RNA dependent effect. Microarray analysis and quantitative RT-PCR demonstrated that MV were shuttling a specific subset of cellular mRNA, such as mRNA associated in the control of transcription, translation, proliferation and apoptosis. When administered in vivo, MV were found to accelerate the morphological and functional recovery of liver in a model of 70% hepatectomy in rats by inducing an hepatocytes proliferation that was abolished by RNase treatment. Using human AGO2 gene, which is shuttled by MV, as a reporter gene, we found the expression of human AGO2 mRNA and protein in the liver of hepatectomized rats treated with MV. This suggest a translation of the MV shuttled mRNA within hepatocytes of treated rats. Conclusion: these results suggest that MV derived from HLSC may activate a proliferative program in remnant hepatocytes after hepatectomy by a horizontal transfer of specific mRNA subsets.
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| Overall design |
MV contained mRNA was submitted to microarray analysis not to define the amount of mRNA but only to define which transcripts were present. Total RNA was prepared from two independent preparation of vesicles. 250, 500 and 1000 ngs from each preparation were transformed in biotin-labeled cRNA. A simple statistical linear model was used to identify transcript signals linearly correlated to the increment of total RNA concentration used to prepare cRNA.
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| Contributor(s) |
Herrera MB, Fonsato V, Gatti S, Deregibus MC, Sordi A, Cantarella D, Calogero RA, Bussolati B, Tetta C, Camussi G |
| Citation(s) |
19650833, 20668554 |
| Submission date |
Apr 06, 2009 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Raffaele A Calogero |
| E-mail(s) |
raffaele.calogero@unito.it
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| Phone |
++39 0116706454
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| Organization name |
University of Torino
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| Department |
Molecular Biotechnology Center
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| Lab |
Bioinformatics and Genomics Unit
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| Street address |
Via Nizza 52
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| City |
Torino |
| State/province |
To |
| ZIP/Postal code |
10126 |
| Country |
Italy |
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| Platforms (1) |
| GPL6884 |
Illumina HumanWG-6 v3.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA115741 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE15569_RAW.tar |
7.9 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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