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Glial cell missing 1(Gcm1) is reduced due to upregulation of miR30b‐30d cluster in the placenta of the BPH/5 mouse model of preeclampsia (PE)
Author(s) -
Zhou Yi,
Woods Ashley K,
Chiang Serena,
Guruju Mallikarjuna R,
Sharma Ram V,
Davisson Robin L
Publication year - 2011
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.25.1_supplement.663.4
We have described a mouse strain (BPH/5) that spontaneously develops fetoplacental defects and cardinal features of PE. Given the importance of miRNAs in regulating gene expression, we tested the hypothesis that miRNA‐mediated changes in Gcm1, a transcription factor required for early placental development, is reduced in BPH/5 fetoplacental units due to upregulation of specific miRNAs. In silico analysis of upregulated miRNA cluster miR‐30b‐miR‐30d, measured by real‐time qPCR analysis in classes of BPH/5 fetoplacental units varying in health status (e10.5; Table), predicted that Gcm1 is a putative target for this cluster. Quantification of Gcm1 expression and its target Syncytin A showed that their expression is significantly decreased in BPH/5 fetoplacental units compared to C57 (Table). To further verify that Gcm1 is a target of miR‐30b and 30d, reporter assays were performed on 3′UTR region of Gcm1 mRNA cloned into a luciferase reporter. The luciferase assays showed that miR‐30b and miR‐30d significantly inhibited reporter activity as compared to negative control (control 1.1±0.08; miR‐30b, 0.65±0.02; miR‐30d, 0.74±0.05; miR‐30b+miR‐30d, 0.53±0.14, p<0.05; n=3). These results suggest that miR30b‐30d‐mediated inhibition of Gcm1 expression may play an important role in the fetoplacental pathology observed in this model.