1,25-(OH(2))D(3) alters the transforming growth factor beta signaling pathway in renal tissue

1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) plays an important role in regulating immune responses, in addition to its effects on bone metabolism. The cytokine transforming growth factor beta (TGF-beta) regulates diverse biological processes, including cellular proliferation and differentiation, immune modulation, and modulation of extracellular matrix deposition. 1,25-(OH)(2)D(3) interacts in vitro with Smad proteins, important regulators of TGF-beta signal transduction. We hypothesized that exogenous 1,25-(OH)(2)D(3) would alter levels of TGF-beta(1) and TGF-beta(1) signaling proteins in renal tissue.

C57BL6 mice and Lewis rats were placed on diets with or without 1,25-(OH)(2)D(3) for 14 days. Renal lysates were examined for TGF-beta(1), vitamin D receptor (VDR), and Smad3 protein levels using a cell proliferation assay and Western blot analysis. Coimmunoprecipitation was used to determine if any interaction between VDR and Smad3 proteins occurs in vivo. Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess messenger RNA (mRNA) levels for all of these molecules.

Vitamin D supplementation decreased VDR and Smad3 protein levels. Coimmunoprecipitation of VDR and Smad3 revealed a Smad3-VDR interaction in vivo. Vitamin D-treated rats had a significant (P = 0.001) reduction in bioactive renal TGF-beta(1). RT-PCR demonstrated no difference in mRNA expression for either VDR or TGF-beta(1).

Our results suggest that vitamin D has a significant effect in regulating levels of bioactive TGF-beta(1) and appears to affect aspects of the TGF-beta(1) signaling system. These effects, in combination with the immunomodulatory actions of vitamin D, may alter the evolution of chronic rejection in renal transplants.