Bestrophin 1 promotes epithelial-to-mesenchymal transition of renal collecting duct cells.
Bestrophin 1 (Best1) controls intracellular Ca(2+) concentration, induces Ca(2+)-activated Cl(-) conductance, and increases proliferation of colon carcinoma cells. Here, we show that expression of Best1 in mouse renal collecting duct (CD) cells causes i) an increase in cell proliferation, ii) a loss of amiloride-sensitive Na(+) absorption, iii) induction of Ca(2+)-dependent Cl(-) conductance (CaCC), and iv) epithelial-to-mesenchymal transition. During conditions of high proliferation or when we exposed CD cells to serum or TGF-beta1, we observed upregulation of Best1, increased CaCC, redistribution of the epithelial-to-mesenchymal transition marker beta-catenin, and upregulation of vimentin. In contrast, suppression of Best1 by RNAi inhibited proliferation, reduced CaCC, and downregulated markers of EMT. CaCC and expression of Best1 were independent of the cell cycle but clearly correlated to cell proliferation and cell density. During renal inflammation in LPS-treated mice or after unilateral ureteral obstruction, we observed transient upregulation of Best1. These data indicate that repression of cell proliferation, CaCC, and expression of Best1 occurs during mesenchymal-to-epithelial transition once CD cells polarize and terminally differentiate. These results may suggest a role for Best1 in renal fibrosis and tissue repair.
Aldehni
Fadi
F
Department of Physiology, University of Regensburg, University Street 31, Regensburg 93053, Germany.
Spitzner
Melanie
M
Martins
Joana Raquel
JR
Barro-Soria
René
R
Schreiber
Rainer
R
Kunzelmann
Karl
K
D000818:Animals; D000075002:Bestrophins; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007473:Ion Channels; D007685:Kidney Tubules, Collecting / Q000166:cytology* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012964:Sodium / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
C491856:Best1 protein, mouse; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D007473:Ion Channels; D008070:Lipopolysaccharides; D014746:Vimentin; D051176:beta Catenin; D012964:Sodium; D002118:Calcium