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- Title
1,25-Dihydroxyvitamin D<sub>3</sub> Stimulates Transforming Growth Factor-β1 Synthesis by Mouse Renal Proximal Tubular Cells.
- Authors
Weinreich, Th.; Landolt, M.; Booy, C.; Wüthrich, R.P.; Binswanger, U.
- Abstract
1,25-Dihydroxyvitamin D3 [1,25-(OH)2 D3] is a secosteroid hormone with effects on cell growth, differentiation and immunoregulatory functions in a number of tissues not primarily involved in mineral metabolism. We recently demonstrated growth-regulating effects of 1,25-(OH)2 D3 on human mesangial cells and proximal tubular cells. To investigate whether 1,25-(OH)2 D3 might also affect the synthesis of cytokines and growth factors in proximal tubular cells, we assessed in the present study the expression and secretion of transforming growth factor-β1 (TGF-β1) in a mouse proximal tubular cell line (MCT) in vitro. TGF-β1 synthesis was measured by a monospecific ELISA in culture supernatant. The secreted TGF-β1 was proven to be biologically active by means of a bioassay system (CCL-64 mink lung epithelial cell proliferation assay). TGF-β1 gene expression was assessed by RT-PCR. To analyze whether TGF-β1 expression mediates the 1,25-(OH)2 D3-induced antiproliferative actions in MCT, proliferation studies in the absence or presence of a blocking monoclonal anti TGF-β1-3 antibody were performed. 1,25-(OH)2 D3 (10-11 to 10-7 M) specifically increased the TGF-β1 protein secretion in MCT with a maximum at 10-8 M. No detectable effect was found with 25 D3 at 10 times higher concentrations. A synthetic 20-epi analogue, MC 1288, increased TGF-β1 secretion up to similar amounts at equimolar concentrations as the natural hormone 1,25-(OH)2 D3. Steady-state TGF-β1 mRNA concentration in MCT was transiently increased by 1,25-(OH)2 D3 between 12 and 24 h, returning to control values at 48 h. Blocking TGF-β1 did not reduce or abrogate the antiproliferative effect of 1,25-(OH)2 D3. In conclusion, 1,25-(OH)2 D3 stimulates TGF-β1 expression in renal proximal tubular cells, a growth factor with anti-inflammatory and profibrotic actions which plays an important role in the development and progression of nephrosclerosis.
- Publication
Kidney & Blood Pressure Research, 1999, Vol 22, Issue 3, p99
- ISSN
1420-4096
- Publication type
Article
- DOI
10.1159/000025914