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Genome‐wide delineation of VEGF‐related genes in the cervix of pregnant rats reveal unexpected candidates
Author(s) -
Mowa Chishimba Nathan,
Li T,
Folkesson H,
Lopez M,
Jesmin S,
Usip S,
Papka R,
Smith D
Publication year - 2006
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.20.5.a1151
Subject(s) - cervix , gene , microarray , vegf receptors , microarray analysis techniques , lipofectamine , microbiology and biotechnology , biology , gene expression , cancer research , genetics , cancer , vector (molecular biology) , recombinant dna
Given that leukocytes, derived from microvasculature, are critical for cervical ripening (CR) and that VEGF, whose levels increase near term, is the key architect of microvascular remodeling, VEGF likely plays vital roles in CR. However, its definite roles in CR are unknown. Here, we use VEGF siRNA and genome‐wide DNA microarray analysis, to decipher VEGF‐related genes in pregnant rat. We used a siRNA‐generating plasmid DNAs targeting VEGF. 40 ug of siRNA, dissolved in Lipofectamine and mixed in a micellar nanocontainer polymer, pluronic block copolymer, were administered to the cervix intravaginally at days 17 and 19 of pregnancy, leading to a 50% reduction in VEGF at day 20, based on RT‐PCR densitometric analysis. Moreover, analysis of microarray data, according to the EASE score, revealed that, not only the gene expression of “hallmark” biological processes of VEGF, such as cell proliferation and motility, circulation, tissues remodeling, heat shock protein activity and cell adhesion molecule activity were altered, but, intriguingly, also of unexpected, but important candidates involved in CR, most notably oxytocin and prostaglandins. These data are novel and important, in that they shed new insights in VEGF's possible roles and mechanisms in cervical events near term, including CR. Support: Appalachian St Univ & NEOUCOM grants.