Vitamin D Actions: The Lung Is a Major Target for Vitamin D, FGF23, and Klotho

Vitamin D is well known for its role as a calcium regulator and in maintenance of phosphate homeostasis in musculoskeletal health, and fibroblast growth factor 23 (FGF23) and its coreceptor α-klotho are known for their roles as regulators of serum phosphate levels. However, apart from these classical actions, recent data point out a relevant role of vitamin D and FGF23/klotho in lung health. The expression of the vitamin D receptor by different cell types in the lung and the fact that those cells respond to vitamin D or can locally produce vitamin D indicate that the lung represents a target for vitamin D actions. Similarly, the presence of the four FGF receptor isoforms in the lung and the ability of FGF23 to stimulate pulmonary cells support the concept that the lung is a target for FGF23 actions, whereas the contribution of klotho is still undetermined. This review will give an overview on how vitamin D or FGF23/klotho may act on the lung and interfere positively or negatively with lung health. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.