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J. Biol. Chem., Vol. 275, Issue 24, 17937-17945, June 16, 2000
From the Department of Biochemistry, University of Texas Health
Science Center, San Antonio, Texas 78284-7600 and the
Bone morphogenetic proteins (BMPs) occupy
important roles during development serving to direct cells through
specific differentiation programs. While several BMPs are essential for
embryonic viability, their significance in mediating intercellular
communication in the context of adult organ systems remains largely
unknown. In the adult rat we characterized the tissue- and
cell-specific transcription and translation of BMP-9. Utilizing a
ribonuclease protection assay, we determined that in the adult animal,
BMP-9 expression occurs predominantly in the liver. Furthermore, we
determined that the non-parenchymal cells of the liver,
i.e. endothelial, Kupffer, and stellate cells, are the
major sources of this message. Western analyses corroborate the
ribonuclease protection assay results, confirming that LEC and KC
contain an abundance of immunoreactive BMP-9. Using
[125I]BMP-9, a receptor with specific binding affinity
for BMP-9 was characterized in primary cultures of hepatic endothelial
cells and Kupffer cells. BMP-9 binding to these cell types was observed to be fully reversible and highly specific for this ligand.
Additionally, we demonstrate that BMP-9 is specifically internalized
upon binding to its receptor. This may represent a novel BMP receptor
and is the first to be characterized in primary cultures of mature
liver non-parenchymal cells. Our results depict BMP-9 as a potential autocrine/paracrine mediator in the hepatic reticuloendothelial system.
Bone Morphogenetic Protein-9
AN AUTOCRINE/PARACRINE CYTOKINE IN THE LIVER*
, and Genetics Institute, Inc.,
Cambridge, Massachusetts 02140
*
This work was supported by National Institutes of Health
Grant DK-19473.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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