Source:http://linkedlifedata.com/resource/pubmed/id/16873554
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2006-11-6
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pubmed:abstractText |
Progranulin (pgrn; granulin-epithelin precursor, PC-cell-derived growth factor, or acrogranin) is a multifunctional secreted glycoprotein implicated in tumorigenesis, development, inflammation, and repair. It is highly expressed in macrophage and monocyte-derived dendritic cells. Here we investigate its regulation in myeloid cells. All-trans retinoic acid (ATRA) increased pgrn mRNA levels in myelomonocytic cells (CD34(+) progenitors; monoblastic U-937; monocytic THP-1; progranulocytic HL-60; macrophage RAW 264.7) but not in nonmyeloid cells tested. Interleukin-4 impaired basal expression of pgrn in U-937. Differentiation agents DMSO, and, in U-937 only, phorbol ester [phorbol 12-myristate,13-acetate (PMA)] elevated pgrn mRNA expression late in differentiation, suggestive of roles for pgrn in more mature terminally differentiated granulocyte/monocytes rather than during growth or differentiation. The response of pgrn mRNA to ATRA differs in U-937 and HL-60 lineages. In U-937, ATRA and chemical differentiation agents greatly increased pgrn mRNA stability, whereas, in HL-60, ATRA accelerated pgrn mRNA turnover. The initial upregulation of pgrn mRNA after stimulation with ATRA was independent of de novo protein synthesis in U-937 but not HL-60. Chemical blockade of nuclear factor-kappaB (NF-kappaB) activation impaired ATRA-stimulated pgrn expression in HL-60 but not U-937, whereas in U-937 it blocked PMA-induced pgrn mRNA expression, suggestive of cell-specific roles for NF-kappaB in determining pgrn mRNA levels. We propose that: 1) ATRA regulates pgrn mRNA levels in myelomonocytic cells; 2) ATRA acts in a cell-specific manner involving the differential control of mRNA stability and differential requirement for NF-kappaB signaling; and 3) elevated pgrn mRNA expression is characteristic of more mature cells and does not stimulate differentiation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0363-6119
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
291
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
R1602-12
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pubmed:meshHeading |
pubmed-meshheading:16873554-Cell Differentiation,
pubmed-meshheading:16873554-Cell Line,
pubmed-meshheading:16873554-Dose-Response Relationship, Radiation,
pubmed-meshheading:16873554-Gene Expression Regulation,
pubmed-meshheading:16873554-Humans,
pubmed-meshheading:16873554-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:16873554-Interleukin-4,
pubmed-meshheading:16873554-Myeloid Cells,
pubmed-meshheading:16873554-Tretinoin
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pubmed:year |
2006
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pubmed:articleTitle |
Regulation of progranulin expression in myeloid cells.
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pubmed:affiliation |
Endocrine Research Laboratories, Department of Medicine, Royal Victoria Hospital, McGill University, 687 Pine Avenue West, Montreal, Quebec, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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