Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription

被引：195

作者：

Aliotta, Jason M. ^{[1
,2
]}

Pereira, Mandy ^{[1
]}

Johnson, Kevin W. ^{[1
]}

de Paz, Nicole ^{[1
]}

Dooner, Mark S. ^{[1
]}

Puente, Napoleon ^{[2
]}

Ayala, Carol ^{[3
]}

Brilliant, Kate ^{[1
]}

Berz, David ^{[1
]}

Lee, David ^{[2
]}

Ramratnam, Bharat ^{[4
]}

McMillan, Paul N. ^{[3
]}

Hixson, Douglas C. ^{[1
]}

Josic, Djuro ^{[5
]}

Quesenberry, Peter J. ^{[1
]}

机构：

[1] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Div Hematol & Oncol, Providence, RI 02903 USA

[2] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Div Pulm Sleep & Crit Care Med, Providence, RI 02903 USA

[3] Rhode Isl Hosp, Div Core Res Labs, Transmiss Electron Microscopy Facil, Providence, RI 02903 USA

[4] Brown Univ, Dept Med, Div Infect Dis, Lab Retrovirol,Warren Alpert Med Sch, Providence, RI 02912 USA

[5] Rhode Isl Hosp, COBRE CCRD, Providence, RI 02903 USA

来源：

EXPERIMENTAL HEMATOLOGY | 2010年 / 38卷 / 03期

基金：

美国国家卫生研究院;

关键词：

HORIZONTAL TRANSFER; PLATELET MICROPARTICLES; MULTIVESICULAR BODIES; PROTEOMIC ANALYSIS; MEMBRANE-VESICLES; EXOSOMES; EXPRESSION; REVEALS; IDENTIFICATION; PROTEINS;

D O I：

10.1016/j.exphem.2010.01.002

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Objective. Microvesicles have been shown to mediate intercellular communication. Previously, we have correlated entry of murine lung-derived microvesicles into murine bone marrow cells with expression of pulmonary epithelial cell-specific messenger RNA (mRNA) in these marrow cells. The present studies establish that entry of lung-derived microvesicles into marrow cells is a prerequisite for marrow expression of pulmonary epithelial cell-derived mRNA. Materials and Methods. Murine bone marrow cells cocultured with rat lung, but separated from them using a cell-impermeable membrane (0.4-mu m pore sire), were analyzed using species-specific printers (for rat or mouse). Results. These studies revealed that surfactant 13 and C mRNA produced by murine marrow cells were of both rat and mouse origin. Similar results were obtained using murine lung cocultured with rat bone marrow cells or when bone marrow cells were analyzed for the presence of Species-Specific albumin mRNA after coculture with rat or murine liver. These studies show that microvesicles both deliver mRNA to marrow cells and mediate marrow cell transcription of tissue-specific mRNA. The latter likely Underlies the longer-term stable change in genetic phenotype that has been observed. We have also observed microRNA in lung-derived microvesicles, and studies with RNase-treated microvesicles indicate that microRNA negatively modulates pulmonary epithelial cell-specific mRNA levels in cocultured marrow cells. In addition, we have also observed tissue-specific expression of brain, heart, and liver mRNA in cocultured marrow cells. suggesting that microvesicle-mediated cellular phenotype change is a universal phenomena. Conclusion. These studies suggest that cellular systems :are more phenotypically labile than previously considered. (C) 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

引用

页码：233 / 245

页数：13

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