1,25-DIHYDROXYVITAMIN-D-3 AND THE SYNTHETIC - VITAMIN-D ANALOG, KH-1060, MODULATE THE GROWTH OF MOUSE PROXIMAL TUBULAR CELLS

Apart from its classical role in bone and mineral metabolism, 1,25-dih ydroxy-vitamin D-3 (1,25-vitamin D-3) has recently been shown to affec t cell growth and differentiation from a variety of tissues primarily not involved in mineral metabolism and to provide immunomodulatory fun ctions. Findings in human mesangial cells in vitro as well as in a rat model of compensatory renal growth in vivo suggest that renal cells a re a target for 1,25-vitamin D-3 In the present study the effects of 1 ,25-vitamin D-3 and a synthetic vitamin D analogue, KH 1060, on prolif eration and protein synthesis were investigated in a mouse proximal tu bular cell line (MCT). 1,25-vitamin D-3 and KH 1060 inhibited cell pro liferation dose dependently (10(-7) to 10(-12) M) and specifically as assessed by H-3-thymidine incorporation (DNA synthesis) and cell count ing. The cellular protein concentration, protein synthesis (H-3-methio nine incorporation) and protein/DNA ratio were not influenced by 1,25- vitamin D-3 and KH 1060. By analyzing c-fos and c-myc expression using semiquantitative RT-PCR, a constant basal expression of both protoonc ogenes, even under serum-free conditions, was found in MCT cells. Phor bol 12-myristate 13-acetate (TPA) further stimulated c-fos and c-myc e xpression, whereas treatment with 1,25-vitamin D-3 (10(-7) M) it had n o effect either in unstimulated or in TPA-stimulated cells. In conclus ion, 1,25-vitamin D-3 and a synthetic vitamin D analogue, KH 1060, pro vide growth-regulating effects on renal proximal tubular cells in vitr o. These effects are not mediated by regulation of c-fos and c-myc. Fu rther studies will have to clarify whether 1,25-vitamin D-3 plays a ph ysiologic role in renal development and growth in vivo.