Ulcerative Colitis associated with a 90% reduced activation of Vitamin D Receptor
Influence of vitamin D receptor signaling and vitamin D on colonic epithelial cell fate decisions in ulcerative colitis
Data from this study was presented in part at the American College of Gastroenterology Annual Meeting, Vancouver, BC, October 20-25, 2023.
Lauge Kellermann1, Stine Lind Hansen2, Grzegorz Maciag2, Agnete Marie Granau1, Jens Vilstrup Johansen3, Joji Marie Teves2,3, Raul Bardini Bressan2, Marianne Terndrup Pedersen3, Christoffer Soendergaard1, Astrid Moeller Baattrup2, Alexander Hammerhpj1, Lene Buhl Riis4, John Gubatan5, Kim Bak Jensen2, Ole Haagen Nielsen1
Note: VDR is a log scale. log of 5.6 is 1/10 of log of 6.6
Background and aims: Epidemiological studies have shown that subnormal levels of vitamin D (25(OH)D) are associated with a more aggravated clinical course of ulcerative colitis (UC). Despite an increased focus on the therapeutic importance of vitamin D and vitamin D receptor (VDR) signaling, the mechanisms underlying the effects of the vitamin D-VDR axis on UC remain elusive. Therefore, we aimed to investigate whether exposure to active vitamin D (1,25(OH)2D3)/VDR signaling in human organoids could influence the maintenance of the colonic epithelium.
Methods: Intestinal VDR expression was studied by immunohistochemistry, RNA expression arrays, and single-cell RNA sequencing of colonic biopsy specimens obtained from patients with UC and healthy individuals. To characterize the functional and transcriptional effects of 1,25(OH)2D3, we used patient-derived colonic organoids. The dependency of VDR was assessed by knocking out the receptor with CRISPR/Cas9.
Results: Our results suggest that 1,25(OH)2D3/VDR stimulation supports differentiation of the colonic epithelium and that impaired 1,25(OH)2D3/VDR signaling thereby may compromise the structure of the intestinal epithelial barrier, leading to flares of UC. Furthermore, a transcriptional response to VDR activity was observed primarily in fully differentiated cells at the top of the colonic crypt, and this response was reduced during flares of UC.
Conclusions: We identified an important role of vitamin D signaling in supporting differentiated cell states in the human colonic epithelium, and thereby maintenance of the intestinal barrier integrity. This makes the vitamin D-VDR signaling axis an interesting target for therapeutic efforts to achieve and maintain remission in patients with UC.
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VitaminDWiki - studies in both categories GUT and VDR
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VitaminDWiki – The Vitamin D Receptor is associated with many health problems
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My wife's UC has been eliminated for years since she started taking the gut VDR activator: Sodium Butyrate
Note: Some diseases protect themselves by deactivating the Vitamin D Receptor
Unknown: UC ==> Reduced VDR OR Reduced VDR==> UC