Thrombopoietin stimulates VEGF release from c-Mpl-expressing cell lines and haematopoietic progenitors.
Vascular endothelial growth factor (VEGF) production was analysed in megakaryocytic cell lines and CD34+ haematopoietic progenitors following treatment with thrombopoietin (TPO). In CMK cells TPO caused a time- and dose-dependent increase in the levels of VEGF released into the medium. A similar effect was observed in UT-7/mpl cells transfected with the TPO receptor c-Mpl, but not in parental UT-7 cells. In CD34+ haematopoietic progenitor cell cultures TPO stimulated VEGF mRNA expression and VEGF protein release. Production of VEGF in CD34+ cultures increased with TPO-induced megakaryocytic differentiation, but not with erythroid or myelomonocytic differentiation induced respectively by erythropoietin and granulocyte-macrophage colony-stimulating factor. These results demonstrate that TPO stimulates VEGF release in c-Mpl-expressing cells and suggest that this process is an integral feature of the megakaryocytic differentiation programme.
Bobik
R
R
Cruciform Project and Department of Medicine, Rayne Institute, University College London, UK.
Hong
Y
Y
Breier
G
G
Martin
J F
JF
Erusalimsky
J D
JD
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D003470:Culture Media; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013926:Thrombopoietin / Q000378:metabolism* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D003470:Culture Media; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C082218:MPL protein, human; D013926:Thrombopoietin