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Modulation of Growth Factor/Cytokine Synthesis and Signaling by 1,25-Dihydroxyvitamin D₃: Implications in Cell Growth and Differentiation

Departments of Medicine (A.G., R.K.), Dermatology (M.R.P.), and Biochemistry and Molecular Biology (M.R.P., R.K.), Mayo Clinic and Foundation, Rochester, Minnesota 55905

Correspondence: Address all correspondence and requests for reprints to: Rajiv Kumar, M.D., Departments of Medicine, Biochemistry and Molecular Biology, Mayo Clinic and Foundation, 200 First Street SW, 911A Guggenheim Building, Rochester, Minnesota 55905. E-mail: rkumar{at}mayo.edu

Distinct from its classic functions in the regulation of calcium and phosphorus metabolism as a systemic hormone, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] is involved in the local control and regulation of cellular growth and differentiation in various tissues, including epidermis (keratinocytes) and bone (osteoblasts and osteoclasts). In this review, the impact of 1,25(OH)₂D₃ on growth factor/cytokine synthesis and signaling is discussed, particularly as it pertains to bone cells and keratinocytes. 1,25(OH)₂D₃ not only regulates growth factor/cytokine synthesis but may also alter growth factor signaling. Recently discovered examples for such interactions are the interactions between the vitamin D receptor and the mothers against decapentaplegic-related proteins that function downstream of TGFß receptors. Inhibitory effects of 1,25(OH)₂D₃ on keratinocytes through TGFß activation and IL-1, IL-6, and IL-8 suppression may provide a rationale for its beneficial effects in the treatment of hyperproliferative skin disorders, whereas stimulatory effects through the epidermal growth factor-related family members and platelet-derived growth factor may be operative in its beneficial effects in skin atrophy and wound healing. Modulation of cytokines and growth factors by 1,25(OH)₂D₃ during bone remodeling plays an important role in the coupling of osteoblastic bone formation with osteoclastic resorption to maintain bone mass.

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