title: Hepatocyte nuclear factor 4 alpha is associated with mesenchymal-epithelial transition in developing kidneys of C57BL/6 mice.
abstract: 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 Hnf4α, the fibroblast cell line with forced expression of Hnf4α protein were analyzed. In this model, it was noted that Hnf4α 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 Hnf4α protein is associated with the initiation of MET in early nephrogenesis.
authors.affiliation: Laboratory of Anatomy, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060–0818, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Ichii
authors.forename: Saori
authors.initials: S
authors.lastname: Otsuka
authors.forename: Yuka
authors.initials: Y
authors.lastname: Namiki
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kon
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000196:embryology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells
chemical_list: D051557:Hepatocyte Nuclear Factor 4