Renal expression of osteopontin and alkaline phosphatase correlates
with bun levels in aged rats.
Liang, C. Tony, and Janice Barnes.
Gerontology Research Center, National Institute on Aging, National
Institutes of Health, 4940 Eastern Avenue, Baltimore, Maryland
21224
APStracts 2:0069F, 1995.
Renal expression of alkaline phosphatase (AP) and osteopontin (OP) in
rats of different age was examined. Northern blot hybridization
showed that AP mRNA was reduced moderately whereas OP mRNA was
stimulated drastically in old rats. Dot blot quantitation analysis
showed that AP mRNA decreased 30% in 24-month as compared to 6-month
rats. In contrast, OP mRNA increased 3.1 and 9.1 fold respectively in
12- and 24-month rats. [beta]-actin mRNA did not change with age.
Blood urea nitrogen (BUN) increased 47% and 187% in 12- and 24-month
rats, respectively. Correlation analysis showed that BUN correlated
negatively with AP mRNA and positively with OP mRNA. No correlation
was observed with [beta]-actin. The expression of these markers was
also examined in femurs. AP and OP mRNAs were marginally reduced in
old bones. To test whether the correlation also exists in other types
of renal insufficiency, we examined these parameters in young rats
infused with PTH. BUN was elevated 3.5 fold whereas AP mRNA decreased
48% and OP mRNA increased 15.3 fold in kidneys of PTH-treated rats.
To elucidate the possible mechanisms which lead to the over
-expression of OP in kidney, we examined the expression of TGF-[beta]1
mRNA. No significant differences in TGF-[beta]1 expression was
observed between young and old rats and control and PTH treated young
rats. Changes in the expression of OP were also visualized by
immunostaining of renal sections. Alterations in the levels of OP and
AP were validated by western blot analysis and enzyme assay of
homogenate, respectively. Histological examination showed lesions of
nephrons in old rats and PTH-infused young rats whereas gross
calcification was observed only in kidneys of PTH-treated young rats.
These findings suggest that some renal proteins, notably OP and AP
can be used as cellular markers for renal dysfuntion associated with
senesence or other renal diseases.
Received 17 January 1995; accepted in final form 24 April 1995.
APS Manuscript Number F11-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.