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Delineation of VEGF‐regulated genes and functions in the cervix of pregnant rodents by DNA microarray analysis
Author(s) -
Boone Thomas Hunter,
Howarth Byran James,
Mowa Chishimba Nathan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.530.2
Subject(s) - biology , microarray , vascular endothelial growth factor , gene expression , gene , microarray analysis techniques , dna microarray , angiogenesis , microbiology and biotechnology , vegf receptors , cancer research , genetics
VEGF‐regulated genes in the cervices of pregnant and non‐pregnant rodents were delineated by DNA microarray and Real Time PCR, after locally altering levels of or action of VEGF using VEGF agents, namely siRNA, VEGF receptor antagonist and mouse VEGF recombinant protein. Tissues were analyzed by genome‐wide DNA microarray analysis, Real‐time and gel‐based PCR, and SEM, to decipher VEGF function during cervical remodeling. Data were analyzed by EASE score (microarray) and ANOVA (Real Time PCR) followed by Scheffe's F ‐test for multiple comparisons. Of the 30,000 genes analyzed, about 4,200 genes were altered in expression by VEGF. Based on EASE score, i.e., grouping of genes according to their biological process, cell component and molecular functions, a number of vascular‐ and non‐vascular‐related processes were found to be regulated by VEGF in the cervix, including immune response, cell proliferation, protein kinase activity, and cell adhesion molecule activity. Of interest, mRNA levels of a select group of genes were altered. VEGF agents also altered mRNA levels of decorin, which is involved in cervical collagen fibrillogenesis, and expression of eNO, PLC and PKC mRNA, critical downstream mediators of VEGF. We show that VEGF may regulate cervical epithelial proliferation, as revealed by SEM. These data are important in that they shed new insights in VEGF's possible roles and mechanisms in cervical events near‐term, including cervical remodeling.