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 and effects of 1,25(OH)2D3 on human mesangial cells (hIVIC), 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 × 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 hIVIC exposed to 1,25(OH)2D3. The data identify actions of 1,25(OH)2D3, a molecule with recently recognized immunoregulatory roles, on hIVIC. The results are consistent with a role of 1,25(OH)2D3 in control of mesangial cell function. © 1991, National Kidney Foundation, Inc.. All rights reserved.