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Publication : Hepatocyte nuclear factor 4 alpha is associated with mesenchymal-epithelial transition in developing kidneys of C57BL/6 mice.

First Author  Kanazawa T Year  2011
Journal  J Vet Med Sci Volume  73
Issue  5 Pages  601-7
PubMed ID  21186337 Mgi Jnum  J:173588
Mgi Id  MGI:5014480 Doi  10.1292/jvms.10-0493
Citation  Kanazawa T, et al. (2011) Hepatocyte nuclear factor 4 alpha is associated with mesenchymal-epithelial transition in developing kidneys of C57BL/6 mice. J Vet Med Sci 73(5):601-7
abstractText  During kidney development, the metanephric mesenchyme (MM) develops into the nephron through mesenchymal-epithelial transition (MET). We have previously reported that knock-down of the expression of hepatocyte nuclear factor 4 alpha (Hnf4a) gene induces failure of cellular organization in the condensed mesenchyme (CM) of cultured embryonic kidneys. To elucidate the details of MET during nephrogenesis, embryonic mouse kidneys were analyzed by electron microscopy, immunohistochemistry, and molecular biology. The findings showed that the intercellular junction, but not the basal lamina, was present in the CM. Additionally, immediately after Hnf4a gene expression, the expression of epithelial genes (Krt8, Tjp1, and Cdh1) increased, and those of mesenchymal genes (Acta1 and Vim) decreased, in the CM compared to the MM. To clarify the relationship between MET and Hnf4alpha, the fibroblast cell line with forced expression of Hnf4alpha protein were analyzed. In this model, it was noted that Hnf4alpha induced increasing epithelial and decreasing mesenchymal gene expression. In these, up-regulation of Pvrl1, -2, and Mllt4 genes which mediate the formation of apico-basal polarity, were found. These results, and those of previous findings, indicate that Hnf4alpha protein is associated with the initiation of MET in early nephrogenesis.
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