Gene regulation of senescence marker protein-30 (SMP30): coordinated up-regulation with tissue maturation and gradual down-regulation with aging

Abstract

Senescence marker protein-30 (SMP30) is a calcium binding protein also called regucalcin. The amounts of SMP30 decrease androgen-independently with aging in the livers of rats. We have studied the expression of SMP30 in livers and kidneys of rats from the embryonic to the senescent stages of life. No transcript was detected in livers or kidneys in day 18 embryos. However, Northern blot analysis showed a marked increase of SMP30 mRNA in livers of neonatal and young rats. The first peak of SMP30 transcript was found in a 5-day-old neonate, in which the amount of mRNA was threefold higher in comparison with 3- to 6.5-month-old adults. The expression of SMP30 protein started to increase from day 7 and rapidly reached a plateau at day 10. The substantial amounts of protein and transcript were maintained in adults up to 3–6.5 months of age. In the kidney, SMP30 mRNA and protein started to increase at day 21 and reached near-maximal levels at day 35. The levels of transcript and protein remained high in adults up to 3 months of age. As the aging process progressed to senescent stages, the levels of transcript and protein decreased significantly in the liver and kidney of aged rats. Therefore, the age-associated decrease of SMP30 in the liver and kidney may be, in a large part, controlled at transcriptional levels. Furthermore, immunohistochemical analysis showed a similar pattern of changes in SMP30 protein expression during neonate, adult and senescent stages in hepatocytes and renal proximal tubular epithelia. The high expression of SMP30 in the tissue-maturing process and adult-hood suggests that SMP30 may be required for the maintenance of highly differentiated hepatic and renal functions.