Post-transcriptional regulation of syndecan-1 expression by cAMP in peritoneal macrophages.
Syndecan-1 is a cell surface heparan sulfate proteoglycan that is proposed to serve in cell-cell adhesion, cell-matrix anchorage, and growth factor signaling. Its expression is temporally and spatially regulated during epithelial-mesenchymal interactions in many developing tissues. In some cases, this regulation appears to be achieved at the level of transcription. However, induction of syndecan-1 expression in the embryonic kidney mesenchyme is suggested to occur at the level of mRNA translation (Vainio, S., M. Jalkanen, M. Bernfield, and L. Saxén. 1992. Dev. Biol. 152:221-232). To identify a system in which the regulatory mechanisms controlling syndecan-1 expression can be studied, cells of the monocyte-macrophage lineage, which regulate the expression of many cell surface receptors, were screened for syndecan-1 expression. The syndecan-1 gene is active in blood monocytes as well as resident and thioglycollate-elicited mouse peritoneal macrophages, but expression of the proteoglycan is regulated at two levels. First, elicited macrophages accumulate nine-fold more syndecan-1 mRNA than do resident macrophages or circulating blood monocytes. Another member of the syndecan family of proteoglycans, syndecan-4, shows a distinct pattern of expression, suggesting that this regulation is specific for syndecan-1. Second, utilization of the mRNA for syndecan-1 production encounters a post-transcriptional block in the elicited macrophages that can be overcome by triggering agents such as E-type prostaglandins or dibutyryl cAMP, which raise intracellular cAMP levels. Dibutyryl cAMP does not induce syndecan-1 expression in resident peritoneal macrophages, which lack a pool of stored mRNA. This suggests that this agent promotes the post-transcriptional utilization of stored syndecan-1 mRNA. The induced proteoglycan appears at the cell surface as a integral of 100-kD heparan sulfate-rich isoform of syndecan-1. This suggests that a cAMP-dependent post-transcriptional control mechanism may be present in a variety of tissues when syndecan-1 expression is regulated.
Yeaman
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Program in Cell and Molecular Biology, University of Wisconsin-Madison 53706-1532.
Rapraeger
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D000818:Animals; D000911:Antibodies, Monoclonal; D001202:Ascitic Fluid / Q000166:cytology; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D009694:Nucleic Acid Precursors / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D053668:Syndecan-1; D053667:Syndecans; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D009694:Nucleic Acid Precursors; D011509:Proteoglycans; D012333:RNA, Messenger; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D003994:Bucladesine; D000242:Cyclic AMP