Actions of 1,25-dihydroxyvitamin D3 on human mesangial cells.
In the present study, we examined specific binding of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by an effects of 1,25(OH)2D3 on human mesangial cells (hMC), obtained from healthy portions of tumor-bearing kidneys. Receptors for 1,25(OH)2D3 were characterized by (1) sucrose density gradient analysis, (2) Scatchard analysis, and (3) DNA affinity of the receptor molecule. Specific binding occurred by a single class of macromolecules, sedimenting with 3.5 S in sucrose density gradients (5% to 20%). Receptors showed high affinity (Kd, 1.39 x 10(-10)), and specific binding capacity (Nmax) of 821 binding sites per cell. 1,25(OH)2D3 (10(-6) to 10(-10)) reduced both DNA synthesis (by [3H]thymidine incorporation) and cell growth (by cell counting) throughout the log-phase and confluence. Further evidence of functional effects of 1,25(OH)2D3 on hMC is provided by ultrastructural studies, which showed rapid increase of electron-dense lysosomal particles in hMC exposed to 1,25(OH)2D3. The data identify actions of 1,25(OH)2D3, a molecule with recently recognized immunoregulatory roles, on hMC. The results are consistent with a role of 1,25(OH)2D3 in control of mesangial cell function.
Weinreich
T
T
Department of Nephrology, University of Heidelberg, Germany.
Merke
J
J
Schönermark
M
M
Reichel
H
H
Diebold
M
M
Hänsch
G M
GM
Ritz
E
E
D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000032:analysis
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D004247:DNA; D002117:Calcitriol