Document Detail


Accelerated expression of senescence associated cell cycle inhibitor p16INK4A in kidneys with glomerular disease.
MedLine Citation:
PMID:  17183247     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cell cycle inhibitor p16(INK4A) (also known as cyclin-dependent kinase inhibitor 2A) is expressed in vivo in many tissues with age. The exposure of certain chronic stresses can trigger p16(INK4A) expression and a senescence-like phenotype. We studied whether p16(INK4A) expression is induced in glomerular disease (GD). We performed p16(INK4A) immunostaining on 35 biopsies with GD, 12 tubulointerstitial nephritis (TIN), and 19 normal live donor kidneys at transplantation. Based on values for 42 normal kidneys, we calculated expected nuclear p16(INK4A) expression for age and compared the observed values in diseased kidneys to those expected for age. In GD, p16(INK4A) expression was strikingly increased in glomerular and interstitial cell nuclei compared to normals and TIN, and could not be attributed to age (P<0.05). By multivariate analyses, GD was independently associated with increased nuclear p16(INK4a) expression in glomeruli (P<0.001) and interstitium (P=0.01). The p16(INK4A) expression in glomerular and interstitial cell nuclei, and tubular cytoplasm was higher in kidneys with proteinuria and with atrophy/fibrosis (P<0.05). Older age was associated with increased nuclear p16(INK4a) expression in tubules (P=0.01), and interstitial inflammation was associated with increased nuclear p16(INK4a) expression in interstitial cells (P=0.001). The p16(INK4a) staining in tubular cytoplasm was increased in both GD and TIN compared to normals (P<0.001), and was not related to age (P>0.05). Thus, kidneys with GD display increased expression of senescence marker p16(INK4A) in glomerular and interstitial cell nuclei compared to kidneys with normal aging or TIN. The findings suggest a role for somatic cell senescence mechanisms in progression of GD.
Authors:
B Sis; A Tasanarong; F Khoshjou; F Dadras; K Solez; P F Halloran
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-12-20
Journal Detail:
Title:  Kidney international     Volume:  71     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-25     Completed Date:  2007-03-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  218-26     Citation Subset:  IM    
Affiliation:
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Age Factors
Aged
Aged, 80 and over
Aging / metabolism*
Biological Markers / analysis
Cell Cycle
Cell Nucleus / chemistry
Cyclin-Dependent Kinase Inhibitor p16 / analysis,  metabolism*
Cytoplasm / chemistry
Female
Glomerulonephritis / metabolism*,  pathology
Humans
Immunohistochemistry
Kidney Glomerulus / chemistry,  metabolism*,  pathology
Male
Middle Aged
Nephritis, Interstitial / metabolism,  pathology
Proteinuria / metabolism
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cyclin-Dependent Kinase Inhibitor p16

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