Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA.
Nutrients. 2022 Dec 7;14(24):5197. doi: 10.3390/nu14245197.
The biological actions of the vitamin D receptor (VDR) have been investigated intensively for over 100 years and has led to the identification of significant insights into the repertoire of its biological actions. These were initially established to be centered on the regulation of calcium transport in the colon and deposition in bone. Beyond these well-known calcemic roles, other roles have emerged in the regulation of cell differentiation processes and have an impact on metabolism. The purpose of the current review is to consider where applying systems biology (SB) approaches may begin to generate a more precise understanding of where the VDR is, and is not, biologically impactful. Two SB approaches have been developed and begun to reveal insight into VDR biological functions. In a top-down SB approach genome-wide scale data are statistically analyzed, and from which a role for the VDR emerges in terms of being a hub in a biological network. Such approaches have confirmed significant roles, for example, in myeloid differentiation and the control of inflammation and innate immunity. In a bottom-up SB approach, current biological understanding is built into a kinetic model which is then applied to existing biological data to explain the function and identify unknown behavior. To date, this has not been applied to the VDR, but has to the related ERα and identified previously unknown mechanisms of control. One arena where applying top-down and bottom-up SB approaches may be informative is in the setting of prostate cancer health disparities.
维生素 D 受体（VDR）的生物学作用已经被深入研究了 100 多年，这使得我们对其生物学作用的范围有了重要的认识。这些作用最初被确定为集中在调节结肠中的钙转运和在骨骼中的沉积。除了这些众所周知的钙调作用外，其他作用也出现在细胞分化过程的调节中，并对代谢产生影响。目前综述的目的是考虑应用系统生物学（SB）方法可能从哪里开始，以更精确地了解 VDR 在生物学上的作用和非作用的位置。已经开发了两种 SB 方法，并开始揭示 VDR 生物学功能的见解。在自上而下的 SB 方法中，对全基因组规模的数据进行统计分析，从而确定 VDR 在生物网络中作为枢纽的作用。这种方法已经证实了其在髓样细胞分化和控制炎症和先天免疫方面的重要作用。在自下而上的 SB 方法中，当前的生物学知识被构建到一个动力学模型中，然后将其应用于现有的生物学数据，以解释其功能并识别未知的行为。到目前为止，这种方法尚未应用于 VDR，但已经应用于相关的 ERα，并确定了以前未知的控制机制。应用自上而下和自下而上的 SB 方法可能会提供信息的一个领域是前列腺癌健康差异。
