Pkd1 regulates immortalized proliferation of renal tubular epithelial cells through p53 induction and JNK activation
J. Clin. Invest. Saori Nishio, et al. 115:910 doi:10.1172/JCI22850 [
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Figure 5Proliferation of Pkd1
–/– cyst epithelial cells. (
A) A kidney from a P17 Pkd1
–/–/LZ
+ mouse was stained with β-gal and counterstained with Nuclear Fast Red. LZ
+ epithelial cells occasionally showed focal hyperplastic features such as micropolyps. Original magnification, ×400. (
B) A kidney froma P12 Pkd1
–/–/LZ
+ mouse was stained with an anti-PCNA. Some cuboidal LZ
+ cyst epithelial cells were accompanied by PCNA expression. Original magnification, ×400. (
C) Expression of p21 and p53 in the kidneys of Pkd1
–/– mice at E16.5 and Pkd1
–/–/LZ
+ mice 1 month of age. The amount of p21 and p53 in kidneys was examined using Western blot. Actin was used as a loading control for protein. Data presented are 1 representative of 4 independent experiments. (
D) Kidneys of P12 Pkd1
–/–/LZ
+ and P12 wild-type mice were stained with anti-p53. Expression of p53 was detected in the flat epithelial cells (white arrowhead) but was significantly decreased in the cuboidal cyst epithelial cells (black arrowheads) of the Pkd1
–/–/LZ
+ mouse. Original magnification, ×400. (
E–
G) The proliferation of cyst epithelial cells in vitro. A single nephron isolated by microdissection from the kidney of a Pkd1
–/–/LZ
+ mouse at E17.5 was cultured in collagen gel for 18 hours. (
F and
G) Higher magnifications of the boxed area above. Both LZ
+ and Pkd1
–/– (LZ
–) cells proliferated. Scale bars: 100 μm.