ABCG2 plays a central role in the dysregulation of 25-hydrovitamin D in Crohn's disease.

Vitamin D (VD) deficiency, as indicated by the main circulating form of VD metabolite 25-hydrovitamin D3 (25(OH)D3), in patients with Crohn's disease (CD) has been well documented, but the reasons for this remain unclear. In this study, 367 patients with CD and 57 healthy individuals who were enrolled, and the association between 25 (OH)D3 level and clinical biochemical characteristics including hepatic and renal functions, inflammatory response was analyzed with binary logistic regression models. VD metabolic enzymes and transporters were screened with bioinformatical analysis and identified with qRT-PCR and western blot. Compared to the healthy controls, serum 25(OH)D3 was significantly reduced in patients with CD, but the protein level of adenosine triphosphate (ATP)-binding cassette efflux transporter G2 (ABCG2) was evidently increased in the ileum and colon. Meanwhile, in lipopolysaccharide (LPS)-treated CaCO2 cells, the mRNA and protein levels of ABCG2 were significantly increased, and the overexpression of ABCG2 obviously promoted 25(OH)D3 efflux, but, Ko143, an ABCG2 inhibitors, substantially prevented the efflux of 25(OH)D3. In addition, in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD model mice, the ABCG2 protein levels were significantly increased in the ileum, colon, kidney and liver, and administration of Ko143 significantly inhibited the efflux of 25 (OH) D3in vivo. All of these findings suggest that VD deficiency in patients with CD may be associated with an abnormal increase in ABCG2 expression, but not directly implicated in hepatic and renal function, and inflammatory response in patients with CD.