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Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis.

The Journal of clinical investigation (2013-08-16)
Weicheng Liu, Yunzi Chen, Maya Aharoni Golan, Maria L Annunziata, Jie Du, Urszula Dougherty, Juan Kong, Mark Musch, Yong Huang, Joel Pekow, Changqing Zheng, Marc Bissonnette, Stephen B Hanauer, Yan Chun Li

The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn's disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD4(+)CD45RB(hi) T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of Vdr-deficient IECs with the hVDR transgene completely rescued Vdr-null mice from severe colitis and death, even though the mice still maintained a hyperresponsive Vdr-deficient immune system. Mechanistically, VDR signaling attenuated PUMA induction in IECs by blocking NF-κB activation, leading to a reduction in IEC apoptosis. Together, these results demonstrate that gut epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this anticolitic activity is independent of nonepithelial immune VDR actions.

Product Number
Product Description

Picrylsulfonic acid solution, 5 % (w/v) in H2O, BioReagent, suitable for determination of primary amines
Picrylsulfonic acid solution, 1 M in H2O