Effects of Vitamin D, PTH and Calcitonin on Osteopontin Expression in Rat Kidney

Han, Ki Hwan; Cha, Jung Ho; Kim, Young Hee; Kim, Wan Young; Kim, Hyang; Kim, Jin

Abstract

Osteopontin(OPN) is a secreted phosphoprotein that is expressed constitutively in the descending thin limb(DTL) and papillary surface epithelium (PSE). Although the function of OPN is not known with certainty, it has been suggested that OPN may play a role in the regulation of calcium-mediated or calcium-dependent processes. The aim of this study was to compare the effects of 1,25-dihydroxyvitamin D3(VitD), parathyroid hormone(PTH) and calcitonin, the hormones involved in the regulation of calcium homeostasis, on renal OPN expression. Three groups of rats were studied:1)acute(single injection of VitD, 200ng/100g BW s.c., 12h before sacrifice) and chronic VitD(daily injection of VitD 50ng/day/100g BW s.c. for 7d). 2) acute(single injection of PTH 50 microgram/100g BW i.p., 30min before sacrifice) and chronic PTH(infusion of PTH 6 microgram/day/100g BW s.c., for 7d via miniosmotic pump). 3) acute(single injection of calcitonin 25U/100g BW i.p., 1h before sacrifice) and chronic calcitonin(infusion of calcitonin 0.2U/ hr/kg BW s.c., for 7d via miniosmotic pump). Each of the study was compared with vehicle-treated animals. Kidneys were processed for immunohistochemistry and OPN expression was examined using a monoclonal antibody to OPN. In vehicle-treated animals, OPN was expressed primarily in DTL and PSE. In the acute VitD and PTH groups, OPN immunoreactivity appeared strongly in proximal tubule, and increased slightly in DTL and PSE. In the chronic VitD and PTH groups, there was a marked increase in OPN immunoreactivity in DTL, PSE, distal convoluted tubule(DCT) and thick ascending limb(TAL) of Henle's loop. Calcitonin groups showed no apparent change. In summary, this study demonstrates that OPN is constitutively expressed in the cells of the DTL and PSE, and induced in proximal tubule(PT), DCT and TAL by vitD and PTH. From these results we conclude that vitD and PTH play an important role in regulation of OPN expression not only in DTL and PSE but also in PT, DCT and TAL.