Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice
Bile acids are major components of bile; they emulsify dietary lipids for efficient digestion and absorption and act as signaling molecules that activate nuclear and membrane receptors. The vitamin D receptor (VDR) is a receptor for the active form of vitamin D and lithocholic acid (LCA), a secondar...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| author | Hitomi Kubota Michiyasu Ishizawa Makoto Kodama Yoshihiro Nagase Shigeaki Kato Makoto Makishima Kenichi Sakurai |
| author_facet | Hitomi Kubota Michiyasu Ishizawa Makoto Kodama Yoshihiro Nagase Shigeaki Kato Makoto Makishima Kenichi Sakurai |
| author_sort | Hitomi Kubota |
| collection | DOAJ |
| description | Bile acids are major components of bile; they emulsify dietary lipids for efficient digestion and absorption and act as signaling molecules that activate nuclear and membrane receptors. The vitamin D receptor (VDR) is a receptor for the active form of vitamin D and lithocholic acid (LCA), a secondary bile acid produced by the intestinal microflora. Unlike other bile acids that enter the enterohepatic circulation, LCA is poorly absorbed in the intestine. Although vitamin D signaling regulates various physiological functions, including calcium metabolism and inflammation/immunity, LCA signaling remains largely unknown. In this study, we investigated the effect of the oral administration of LCA on colitis in a mouse model using dextran sulfate sodium (DSS). Oral LCA decreased the disease activity of colitis in the early phase, which is a phenotype associated with the suppression of histological injury, such as inflammatory cell infiltration and goblet cell loss. These protective effects of LCA were abolished in VDR-deleted mice. LCA decreased the expression of inflammatory cytokine genes, but this effect was at least partly observed in VDR-deleted mice. The pharmacological effect of LCA on colitis was not associated with hypercalcemia, an adverse effect induced by vitamin D compounds. Therefore, LCA suppresses DSS-induced intestinal injury in its action as a VDR ligand. |
| first_indexed | 2024-03-11T08:43:16Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:43:16Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-af4f50f2889f4fe09ba375553875e6e32023-11-16T21:01:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244351710.3390/ijms24043517Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in MiceHitomi Kubota0Michiyasu Ishizawa1Makoto Kodama2Yoshihiro Nagase3Shigeaki Kato4Makoto Makishima5Kenichi Sakurai6Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, JapanDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, JapanDepartment of Pathology, Tokyo Yamate Medical Center, 3-22-1 Hyakunin-cho, Shinjuku-ku, Tokyo 169-0073, JapanDepartment of Pathology, Tokyo Yamate Medical Center, 3-22-1 Hyakunin-cho, Shinjuku-ku, Tokyo 169-0073, JapanGraduate School of Science and Technology, Iryo Sosei University, 5-5-1 Iino, Chuodai, Iwaki, Fukushima 970-8044, JapanDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, JapanDepartment of Surgery, The Nippon Dental University School of Life Dentistry, 2-3-16 Fujimi, Chiyoda-ku, Tokyo 102-8158, JapanBile acids are major components of bile; they emulsify dietary lipids for efficient digestion and absorption and act as signaling molecules that activate nuclear and membrane receptors. The vitamin D receptor (VDR) is a receptor for the active form of vitamin D and lithocholic acid (LCA), a secondary bile acid produced by the intestinal microflora. Unlike other bile acids that enter the enterohepatic circulation, LCA is poorly absorbed in the intestine. Although vitamin D signaling regulates various physiological functions, including calcium metabolism and inflammation/immunity, LCA signaling remains largely unknown. In this study, we investigated the effect of the oral administration of LCA on colitis in a mouse model using dextran sulfate sodium (DSS). Oral LCA decreased the disease activity of colitis in the early phase, which is a phenotype associated with the suppression of histological injury, such as inflammatory cell infiltration and goblet cell loss. These protective effects of LCA were abolished in VDR-deleted mice. LCA decreased the expression of inflammatory cytokine genes, but this effect was at least partly observed in VDR-deleted mice. The pharmacological effect of LCA on colitis was not associated with hypercalcemia, an adverse effect induced by vitamin D compounds. Therefore, LCA suppresses DSS-induced intestinal injury in its action as a VDR ligand.https://www.mdpi.com/1422-0067/24/4/3517vitamin D receptorlithocholic acidbile acidinflammatory bowel diseasedextran sulfate sodiumintestinal mucosal injury |
| spellingShingle | Hitomi Kubota Michiyasu Ishizawa Makoto Kodama Yoshihiro Nagase Shigeaki Kato Makoto Makishima Kenichi Sakurai Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice International Journal of Molecular Sciences vitamin D receptor lithocholic acid bile acid inflammatory bowel disease dextran sulfate sodium intestinal mucosal injury |
| title | Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice |
| title_full | Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice |
| title_fullStr | Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice |
| title_full_unstemmed | Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice |
| title_short | Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice |
| title_sort | vitamin d receptor mediates attenuating effect of lithocholic acid on dextran sulfate sodium induced colitis in mice |
| topic | vitamin D receptor lithocholic acid bile acid inflammatory bowel disease dextran sulfate sodium intestinal mucosal injury |
| url | https://www.mdpi.com/1422-0067/24/4/3517 |
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