IGF-1, PDGF and CD18 are adherence-responsive genes: regulation during monocyte differentiation.
Unstimulated mononuclear cells express IGF-1, PDGF-A and PDGF-B mRNA, but not a number of other genes coding for growth factors or cytokines, as we demonstrated previously. The main focus of the present investigation was to compare gene expression of mononuclear cells unstimulated in suspension with gene expression of monocytes stimulated by adherence. mRNA levels of IGF-1-A and -B, PDGF-A, -B, PD-ECGF, basic FGF, acidic FGF, TGF-alpha, TGF-beta 1, and IGF-2 were sought for and quantified with our sensitive RT-PCR method (3n-PCR). The respective mRNAs of basic FGF, acidic FGF, TGF-alpha and IGF-2 were not detected, independent of the culture conditions. In suspension culture, mRNA levels of IGF-1A and -B, PDGF-A, -B, and CD18 remained unchanged. Monocyte adherence regulated IGF-1A, PDGF-A, and -B mRNA levels. In parallel, mRNA levels of the monocyte adhesion molecule CD18 increased rapidly (4.5-fold). In contrast, independent of the presence of an adherence stimulus, the mRNAs for the cytoskeletal structure protein beta-actin and PD-ECGF remained constant, whereas mRNA for growth factors TGF-beta 1 and IGF-1B, respectively, was increased. Thus, monocyte adherence selectively regulates IGF-1, PDGF-A, PDGF-B and CD18 mRNAs (adherence-responsive genes) in a coordinated manner. This led us to identify two novel consensus elements within their respective functional promoters. Both motifs, an 11 bp purine-rich sequence and a 13 bp pyrimidine-rich segment, respectively, are absent from the genes that were not specifically activated by adherence. The identified elements are potential binding sites for transcription factors that may define a common basis for the regulation of the adherence-responsive genes IGF-1A, PDGF-A, PDGF-B and CD18.
Jendraschak
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E
Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians Universität, Munich, Germany.
Kaminski
W E
WE
Kiefl
R
R
von Schacky
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C
D000199:Actins / Q000235:genetics; D018821:CD18 Antigens / Q000096:biosynthesis / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D016384:Consensus Sequence; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D000199:Actins; D018821:CD18 Antigens; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D013939:Thymidine Phosphorylase