Sustained cell proliferation of renal epithelial cells in mice with inv mutation.
A tubule system is an important component of the nephron, which is the structural and functional unit of the kidney. Expansion of renal tubules results in renal cysts. Hereditary forms of renal cystic diseases suggest that tubular size is determined genetically. The inv was discovered as a mutant with renal cysts and situs inversus. Inv/inv, inv deltaC::GFP (inv deltaC) mouse was created by the introduction of the inv gene lacking the C-terminus (inv deltaC) into inv/inv mice. The mouse develops multiple renal cysts without situs abnormality, giving us an opportunity to study inv function in renal tubular structure maintenance. In the present study, we showed that inv suppresses cyst progression in a dose-dependent manner and that the inv deltaC cystic kidneys showed increased cell proliferation and apoptosis. Cell cycle regulators for G1-S progression were activated in the cystic kidney. Furthermore, cDNA microarray and semiquantitative RT-PCR analysis showed that growth-related genes maintained a high level of expression in the cystic kidney at 4 weeks of age whereas they were decreased in control kidneys, suggesting that cells in inv deltaC kidney are still active in the cell cycle. One of the inv protein functions may provide a stop signal for renal epithelial cell proliferation.
Sugiyama
Noriyuki
N
Department of Anatomy and Developmental Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yokoyama
Takahiko
T
D000483:Alleles; D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000473:pathology; D006133:Growth Substances / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D007684:Kidney Tubules / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology
D018797:Cell Cycle Proteins; D006133:Growth Substances