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Alterations in miRNA‐mediated regulation of thrombospin‐2 in developing placenta of the BPH/5 mouse model of pre‐eclampsia (PE)
Author(s) -
Zhou Yi,
Guruju Mallikarjuna R,
Woods Ashley K,
Sharma Ram V,
Davisson Robin L
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.630.2
Subject(s) - microrna , placenta , biology , gene expression , andrology , endocrinology , gene , bioinformatics , medicine , fetus , pregnancy , genetics
We have recently shown severe fetoplacental abnormalities in the BPH/5 model of PE. Given the importance of miRNAs in regulating gene expression during embryonic development, we hypothesized that changes in miRNA expression in developing placenta of BPH/5 may be involved in fetoplacental defects observed in this model. We employed miRNA microarrays to analyze whole genome miRNA expression in feto‐placental units from BPH/5 (e10.5) over three classes of phenotype severity. Ninety‐four miRNAs were differentially expressed in BPH/5 feto‐placental units compared to C57 controls (fold change >1.5, p<0.05, n=3). miR‐467b and miR‐136 were down‐regulated and validated by real time RT‐PCR (Table 1). miRNA target prediction identified thrombospdin‐2 (Thbs‐2) as a target gene of miR‐467b and miR‐136. Western analysis showed a significant increase Thbs‐2 levels in all three classes of BPH/5 fetoplacental units vs C57 (Table 1). These results suggest that increased expression of Thbs‐2 in BPH/5 placentas due to decreased miRNA‐mediated post‐transcriptional repression may be inhibiting angiogenesis, ultimately leading to fetoplacental abnormalities observed in this model of PE. Table 1. miR‐467b and miR‐136 miRNA and Thrombospodin‐2 protein expression in different classes of BPH/5 feto‐placental unit compared to C57 *<0.05 vs. C57