Transition of kidney tubule cells to a senescent phenotype in early experimental
Authors Satriano J, Mansoury H, Deng A, Sharma K, Vallon V, Blantz RC, Thomson SC
Submitted By Kumar Sharma on 5/2/2011
Status Published
Journal American journal of physiology. Cell physiology
Year 2010
Date Published 8/1/2010
Volume : Pages 299 : C374 - C380
PubMed Reference 20505038
Abstract Diabetic nephropathy is the commonest cause of end-stage renal disease.
Inordinate kidney growth and glomerular hyperfiltration at the very early stages
of diabetes are putative antecedents to this disease. The kidney is the only
organ that grows larger with the onset of diabetes mellitus, yet there remains
confusion about the mechanism and significance of this growth. Here we show that
kidney proximal tubule cells in culture transition to senescence in response to
oxidative stress. We further determine the temporal expression of G(1) phase
cell cycle components in rat kidney cortex at days 4 and 10 of streptozotocin
diabetes to evaluate changes in this growth response. In diabetic rats we
observe increases in kidney weight-to-body weight ratios correlating with
increases in expression of the growth-related proteins in the kidney at day 4
after induction of diabetes. However, at day 10 we find a decrease in this
profile in diabetic animals coincident with increased cyclin-dependent kinase
inhibitor expressions. We observe no change in caspase-3 expression in the
diabetic kidneys at these early time points; however, diabetic animals
demonstrate reduced kidney connexin 43 and increased plasminogen activator
inhibitor-1 expressions and increased senescence-associated beta-galactosidase
activity in cortical tubules. In summary, diabetic kidneys exhibit an early
temporal induction of growth phase components followed by their suppression
concurrent with the induction of cyclin-dependent kinase inhibitors and markers
of senescence. These data delineate a phenotypic change in cortical tubules
early in the pathogenesis of diabetes that may contribute to further downstream
complications of the disease.

Investigators with authorship
Kumar SharmaUniversity of California San Diego