Renal expression of osteopontin and alkaline phosphatase correlates with BUN levels in aged rats.
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-compared with 6-mo-old rats. In contrast, OP mRNA increased 3.1- and 9.1-fold, respectively, in 12- and 24-mo-old rats. beta-Actin mRNA did not change with age. Blood urea nitrogen (BUN) increased 47 and 187% in 12- and 24-mo-old 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 parathyroid hormone (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 that lead to the overexpression of OP in kidney, we examined the expression of transforming growth factor-beta 1 (TGF-beta 1) mRNA. No significant differences in TGF-beta 1 expression were 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Liang
C T
CT
Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Barnes
J
J
D000375:Aging / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053495:Osteopontin; D010281:Parathyroid Hormone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics
D010281:Parathyroid Hormone; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D016212:Transforming Growth Factor beta; D053495:Osteopontin; D000469:Alkaline Phosphatase