Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Differentiation
-
Cell Line
-
Cells, Cultured
-
Culture Media
-
Endothelial Growth Factors / biosynthesis
-
Endothelial Growth Factors / genetics
-
Endothelial Growth Factors / metabolism*
-
Gene Expression
-
Hematopoietic Stem Cells / cytology
-
Hematopoietic Stem Cells / drug effects*
-
Hematopoietic Stem Cells / metabolism
-
Humans
-
Lymphokines / biosynthesis
-
Lymphokines / genetics
-
Lymphokines / metabolism*
-
Megakaryocytes / cytology
-
Megakaryocytes / drug effects*
-
Megakaryocytes / metabolism
-
Neoplasm Proteins*
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / metabolism*
-
RNA, Messenger
-
Receptors, Cytokine*
-
Receptors, Immunologic / genetics
-
Receptors, Immunologic / metabolism*
-
Receptors, Thrombopoietin
-
Recombinant Proteins / metabolism
-
Recombinant Proteins / pharmacology
-
Thrombopoietin / metabolism*
-
Thrombopoietin / pharmacology
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factors
Substances
-
Culture Media
-
Endothelial Growth Factors
-
Lymphokines
-
Neoplasm Proteins
-
Proto-Oncogene Proteins
-
RNA, Messenger
-
Receptors, Cytokine
-
Receptors, Immunologic
-
Receptors, Thrombopoietin
-
Recombinant Proteins
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factors
-
MPL protein, human
-
Thrombopoietin