VEGF-A and serum withdrawal induced changes in the transcript profile in human endometrial endothelial cells.
The changes in transcript profile induced by vascular endothelial growth factor (VEGF-A) and serum withdrawal in primary human endometrial endothelial cells (ECs) were investigated using microarrays, gene ontology and pathway analysis. Vascular endothelial growth factor A altered the levels of transcripts involved in angiogenesis, cell survival, and apoptosis, including up-and downregulation of AKT1, BAD, MIF, and IGFBP3 and ANGPT2, respectively. Serum deprivation induced downregulation of cell-cycle-related transcripts such as mitosis regulators CDC20 and SPC25. Of the transcripts regulated by both VEGF-A and partial serum deprivation, remarkably 88 of 89 showed reciprocal regulation (p < 1 x 10(-49)). These are predominantly cell-fate-associated transcripts and this novel observation suggests that endometrial ECs may be particularly dependant on the levels of these transcripts. Our results show that in addition to the known role of VEGF-A as an EC growth and survival promoter, it also regulates apoptosis-related messenger RNAs (mRNAs), many of which were reciprocally regulated following serum withdrawal.
Moberg
Christian
C
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden. christian.moberg@kbh.uu.se
Catalano
Rob D
RD
Charnock-Jones
D Stephen
DS
Olovsson
Matts
M
D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D018919:Neovascularization, Physiologic; D020411:Oligonucleotide Array Sequence Analysis; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
D016895:Culture Media, Serum-Free; D042461:Vascular Endothelial Growth Factor A