Gurlek Alper, Pittelkow Mark R, Kumar Rajiv
Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Endocr Rev. 2002 Dec;23(6):763-86. doi: 10.1210/er.2001-0044.
Distinct from its classic functions in the regulation of calcium and phosphorus metabolism as a systemic hormone, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] 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 1alpha,25(OH)(2)D(3) on growth factor/cytokine synthesis and signaling is discussed, particularly as it pertains to bone cells and keratinocytes. 1alpha,25(OH)(2)D(3) 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 TGFbeta receptors. Inhibitory effects of 1alpha,25(OH)(2)D(3) on keratinocytes through TGFbeta activation and IL-1alpha, 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 1alpha,25(OH)(2)D(3) during bone remodeling plays an important role in the coupling of osteoblastic bone formation with osteoclastic resorption to maintain bone mass.
与作为一种全身性激素在调节钙和磷代谢方面的经典功能不同，1α,25-二羟基维生素D(3)[1α,25(OH)₂D(3)]参与了包括表皮（角质形成细胞）和骨骼（成骨细胞和破骨细胞）在内的各种组织中细胞生长和分化的局部控制与调节。在这篇综述中，讨论了1α,25(OH)₂D(3)对生长因子/细胞因子合成和信号传导的影响，特别是与骨细胞和角质形成细胞相关的影响。1α,25(OH)₂D(3)不仅调节生长因子/细胞因子的合成，还可能改变生长因子信号传导。最近发现的此类相互作用的例子是维生素D受体与在TGFβ受体下游起作用的抗五肢瘫相关蛋白之间的相互作用。1α,25(OH)₂D(3)通过激活TGFβ以及抑制IL-1α、IL-6和IL-8对角质形成细胞产生的抑制作用，可能为其在治疗过度增殖性皮肤病中的有益作用提供了理论依据，而通过表皮生长因子相关家族成员和血小板衍生生长因子产生的刺激作用可能在其对皮肤萎缩和伤口愈合的有益作用中发挥作用。在骨重塑过程中，1α,25(OH)₂D(3)对细胞因子和生长因子的调节在成骨细胞骨形成与破骨细胞吸收的偶联以维持骨量方面起着重要作用。
