The transcription factor Dach1 is essential for podocyte function
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The transcription factor Dach1 is essential for podocyte function. / Endlich, Nicole; Kliewe, Felix; Kindt, Frances; Schmidt, Katharina; Kotb, Ahmed M; Artelt, Nadine; Lindenmeyer, Maja T; Cohen, Clemens D; Döring, Franziska; Kuss, Andreas W; Amann, Kerstin; Moeller, Marcus J; Kabgani, Nazanin; Blumenthal, Antje; Endlich, Karlhans.
In: J CELL MOL MED, Vol. 22, No. 5, 05.2018, p. 2656-2669.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The transcription factor Dach1 is essential for podocyte function
AU - Endlich, Nicole
AU - Kliewe, Felix
AU - Kindt, Frances
AU - Schmidt, Katharina
AU - Kotb, Ahmed M
AU - Artelt, Nadine
AU - Lindenmeyer, Maja T
AU - Cohen, Clemens D
AU - Döring, Franziska
AU - Kuss, Andreas W
AU - Amann, Kerstin
AU - Moeller, Marcus J
AU - Kabgani, Nazanin
AU - Blumenthal, Antje
AU - Endlich, Karlhans
N1 - © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
PY - 2018/5
Y1 - 2018/5
N2 - Dedifferentiation and loss of podocytes are the major cause of chronic kidney disease. Dach1, a transcription factor that is essential for cell fate, was found in genome-wide association studies to be associated with the glomerular filtration rate. We found that podocytes express high levels of Dach1 in vivo and to a much lower extent in vitro. Parietal epithelial cells (PECs) that are still under debate to be a type of progenitor cell for podocytes expressed Dach1 only at low levels. The transfection of PECs with a plasmid encoding for Dach1 induced the expression of synaptopodin, a podocyte-specific protein, demonstrated by immunocytochemistry and Western blot. Furthermore, synaptopodin was located along actin fibres in a punctate pattern in Dach1-expressing PECs comparable with differentiated podocytes. Moreover, dedifferentiating podocytes of isolated glomeruli showed a significant reduction in the expression of Dach1 together with synaptopodin after 9 days in cell culture. To study the role of Dach1 in vivo, we used the zebrafish larva as an animal model. Knockdown of the zebrafish ortholog Dachd by morpholino injection into fertilized eggs resulted in a severe renal phenotype. The glomeruli of the zebrafish larvae showed morphological changes of the glomerulus accompanied by down-regulation of nephrin and leakage of the filtration barrier. Interestingly, glomeruli of biopsies from patients suffering from diabetic nephropathy showed also a significant reduction of Dach1 and synaptopodin in contrast to control biopsies. Taken together, Dach1 is a transcription factor that is important for podocyte differentiation and proper kidney function.
AB - Dedifferentiation and loss of podocytes are the major cause of chronic kidney disease. Dach1, a transcription factor that is essential for cell fate, was found in genome-wide association studies to be associated with the glomerular filtration rate. We found that podocytes express high levels of Dach1 in vivo and to a much lower extent in vitro. Parietal epithelial cells (PECs) that are still under debate to be a type of progenitor cell for podocytes expressed Dach1 only at low levels. The transfection of PECs with a plasmid encoding for Dach1 induced the expression of synaptopodin, a podocyte-specific protein, demonstrated by immunocytochemistry and Western blot. Furthermore, synaptopodin was located along actin fibres in a punctate pattern in Dach1-expressing PECs comparable with differentiated podocytes. Moreover, dedifferentiating podocytes of isolated glomeruli showed a significant reduction in the expression of Dach1 together with synaptopodin after 9 days in cell culture. To study the role of Dach1 in vivo, we used the zebrafish larva as an animal model. Knockdown of the zebrafish ortholog Dachd by morpholino injection into fertilized eggs resulted in a severe renal phenotype. The glomeruli of the zebrafish larvae showed morphological changes of the glomerulus accompanied by down-regulation of nephrin and leakage of the filtration barrier. Interestingly, glomeruli of biopsies from patients suffering from diabetic nephropathy showed also a significant reduction of Dach1 and synaptopodin in contrast to control biopsies. Taken together, Dach1 is a transcription factor that is important for podocyte differentiation and proper kidney function.
KW - Journal Article
U2 - 10.1111/jcmm.13544
DO - 10.1111/jcmm.13544
M3 - SCORING: Journal article
C2 - 29498212
VL - 22
SP - 2656
EP - 2669
JO - J CELL MOL MED
JF - J CELL MOL MED
SN - 1582-1838
IS - 5
ER -
