Ligand-Dependent Actions of the Vitamin D Receptor Are Required for Activation of TGF-Beta Signaling During the Inflammatory Response to Cutaneous Injury

The study investigated the role of the vitamin D receptor (VDR) in the inflammatory response to skin injury, focusing on its ligand-dependent actions. Using control, VDR knockout, and vitamin D-deficient mice, researchers found that the absence of VDR or its ligand impaired the dermal response to injury, specifically affecting macrophage recruitment and granulation tissue formation, although neutrophil recruitment remained unaffected. The study revealed that the absence of VDR or its ligand disrupted TGF-β signaling, evidenced by decreased monocyte chemotactic protein-1 expression and reduced Smad-3 phosphorylation. These findings indicated that the liganded VDR is crucial for interacting with the TGF-β signaling pathway to ensure a normal inflammatory response to cutaneous injury.