Identification of transcripts specific for physiological gene activation by platelet-derived growth factor (PDGF)-B in intact brain tissue.
Platelet-derived growth factor-B (PDGF-B) and its receptors play essential roles in the complex process of blood vessel maturation and they therefore constitute promising targets for therapeutic strategies against blood vessel-related diseases. Additionally, they are involved in the autocrine stimulation of tumor cells and have been suggested to regulate tumor stroma fibroblasts. Our study aimed to identify genes that are regulated directly by PDGF-B, or indirectly via the recruitment of perivascular cells, in the context of an intact tissue. We used a subtractive cloning technique to compare gene transcription in the brains of wild-type (WT) mice and syngenic mice deficient of PDGF-B leading to a defect in the recruitment of perivascular cells. The resulting 147 differentially expressed sequences contained early and late PDGF-B target genes, and genes implicated in blood vessel maturation-related pathways. Additionally, gene clusters for specific biological processes such as cell migration and intracellular transport were identified. Of eight randomly selected sequences, six were found expressed in cultured cells of mesenchymal origin, two of them inducible by exogenous PDGF-BB. The collection of cDNA presented here provides insights into the changes provoked by the removal of one growth factor of a complete tissue and might be the basis for the identification of novel players in the complex process of blood vessel maturation.
Renner
Oliver
O
Experimental Therapeutics Programme, Spanish National Cancer Centre, E-28029 Madrid, Spain. orenner@cnio.es
Romero
Lourdes
L
Carnero
Amancio
A
Betsholtz
Christer
C
Euler
Monika
M
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D020574:Proto-Oncogene Proteins c-sis / Q000172:deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D018076:DNA, Complementary; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger