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Intestinal vitamin D receptor signaling ameliorates dextran sulfate sodium‐induced colitis by suppressing necroptosis of intestinal epithelial cells
Author(s) -
Shi Yongyan,
Cui Xuewei,
Sun Yanli,
Zhao Qun,
Liu Tianjing
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000143rrr
Subject(s) - necroptosis , inflammatory bowel disease , calcitriol receptor , colitis , ripk1 , chemistry , intestinal mucosa , signal transduction , cancer research , tumor necrosis factor alpha , microbiology and biotechnology , pharmacology , receptor , medicine , biology , biochemistry , programmed cell death , apoptosis , disease
Vitamin D status is closely related to inflammatory bowel disease (IBD), but the mechanism has not been fully elucidated. This study explored the effect of intestinal vitamin D signaling on necroptosis and the underlying mechanism in colitis. Serum 25(OH)D levels and the expression of necroptotic proteins were examined in patients with IBD. Colitis was induced in an intestinal‐specific hVDR transgenic model, and the gross manifestation, histological integrity, and intestinal barrier function were tested. The findings were further confirmed in vitro. Immunoprecipitation and colocalization were performed to investigate the association between the vitamin D receptor and necroptotic proteins. We found that serum 25(OH)D decreased in patients with IBD, while the expression of necroptotic proteins increased. The intestinal hVDR transgenic model could largely ameliorate the structural destruction, restore barrier dysfunction, and suppress necroptosis caused by DSS. This was probably achieved by binding to RIPK1/3 necrosomes, as we observed decreased RIPK1/3 necrosome formation and increased VDR expression in the cytosol. This study demonstrated an inhibitory effect of the intestinal vitamin D signaling pathway on necroptosis in DSS‐induced colitis. The vitamin D receptor shifts from the nucleus to the cytosol to impede the formation of RIPK1/3. Our findings may offer some theoretical basis for a novel treatment of IBD in clinical practice.