1,25-dihydroxyvitamin D3 and the synthetic vitamin D analogue, KH 1060, modulate the growth of mouse proximal tubular cells.
Apart from its classical role in bone and mineral metabolism, 1,25-dihydroxyvitamin D3 (1,25-vitamin D3) has recently been shown to affect cell growth and differentiation from a variety of tissues primarily not involved in mineral metabolism and to provide immunomodulatory functions. Findings in human mesangial cells in vitro as well as in rat model of compensatory renal growth in vivo suggest that renal cells are a target for 1,25-vitamin D3. In the present study the effects of 1,25-vitamin D3 and a synthetic vitamin D analogue, KH 1060, on proliferation and protein synthesis were investigated in a mouse proximal tubular cell line (MCT). 1,25-vitamin D3 and KH 1060 inhibited cell proliferation dose dependently (10(-7) to 10(-12) M) and specifically as assessed by 3H-thymidine incorporation (DNA synthesis) and cell counting. The cellular protein concentration, protein synthesis (3H-methionine incorporation) and protein/DNA ratio were not influenced by 1,25-vitamin D3 and KH 1060. By analyzing c-fos and c-myc expression using semiquantitative RT-PCR, a constant basal expression of both protooncogenes, even under serum-free conditions, was found in MCT cells. Phorbol 12-myristate 13-acetate (TPA) further stimulated c-fos and c-myc expression, whereas treatment with 1,25-vitamin D3 (10(-7) M) it had no effect either in unstimulated or in TPA-stimulated cells. In conclusion, 1,25-vitamin D3 and a synthetic vitamin D analogue, KH 1060, provide growth-regulating effects on renal proximal tubular cells in vitro. These effects are not mediated by regulation of c-fos and c-myc. Further studies will have to clarify whether 1,25-vitamin D3 plays a physiologic role in renal development and growth in vivo.
Weinreich
T
T
Department of Internal Medicine, University Hospital Zürich, Switzerland.
Müller
A
A
Wüthrich
R P
RP
Booy
C
C
Binswanger
U
U
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D016259:Genes, myc; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D051381:Rats
D000970:Antineoplastic Agents; C074279:KH 1060; D002117:Calcitriol