Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier - PubMed (original) (raw)
. 2008 Jan;294(1):G208-16.
doi: 10.1152/ajpgi.00398.2007. Epub 2007 Oct 25.
Affiliations
- PMID: 17962355
- DOI: 10.1152/ajpgi.00398.2007
Free article
Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier
Juan Kong et al. Am J Physiol Gastrointest Liver Physiol. 2008 Jan.
Free article
Abstract
Emerging evidence supports a pathological link between vitamin D deficiency and the risk of inflammatory bowel disease (IBD). To explore the mechanism we used the dextran sulfate sodium (DSS)-induced colitis model to investigate the role of the vitamin D receptor (VDR) in mucosal barrier homeostasis. While VDR(+/+) mice were mostly resistant to 2.5% DSS, VDR(-/-) mice developed severe diarrhea, rectal bleeding, and marked body weight loss, leading to death in 2 wk. Histological examination revealed extensive ulceration and impaired wound healing in the colonic epithelium of DSS-treated VDR(-/-) mice. Severe ulceration in VDR(-/-) mice was preceded by a greater loss of intestinal transepithelial electric resistance (TER) compared with VDR(+/+) mice. Confocal and electron microscopy (EM) revealed severe disruption in epithelial junctions in VDR(-/-) mice after 3-day DSS treatment. Therefore, VDR(-/-) mice were much more susceptible to DSS-induced mucosal injury than VDR(+/+) mice. In cell cultures, 1,25-dihydroxy-vitamin D(3) [1,25(OH)(2)D(3)] markedly enhanced tight junctions formed by Caco-2 monolayers by increasing junction protein expression and TER and preserved the structural integrity of tight junctions in the presence of DSS. VDR knockdown with small interfering (si)RNA reduced the junction proteins and TER in Caco-2 monolayers. 1,25(OH)(2)D(3) can also stimulate epithelial cell migration in vitro. These observations suggest that VDR plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium. Therefore, vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD.
Similar articles
- Protective role of 1,25(OH)2 vitamin D3 in the mucosal injury and epithelial barrier disruption in DSS-induced acute colitis in mice.
Zhao H, Zhang H, Wu H, Li H, Liu L, Guo J, Li C, Shih DQ, Zhang X. Zhao H, et al. BMC Gastroenterol. 2012 May 30;12:57. doi: 10.1186/1471-230X-12-57. BMC Gastroenterol. 2012. PMID: 22647055 Free PMC article. - Loss of the tight junction protein ZO-1 in dextran sulfate sodium induced colitis.
Poritz LS, Garver KI, Green C, Fitzpatrick L, Ruggiero F, Koltun WA. Poritz LS, et al. J Surg Res. 2007 Jun 1;140(1):12-9. doi: 10.1016/j.jss.2006.07.050. Epub 2007 Apr 6. J Surg Res. 2007. PMID: 17418867 - R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice.
Zhao J, de Vera J, Narushima S, Beck EX, Palencia S, Shinkawa P, Kim KA, Liu Y, Levy MD, Berg DJ, Abo A, Funk WD. Zhao J, et al. Gastroenterology. 2007 Apr;132(4):1331-43. doi: 10.1053/j.gastro.2007.02.001. Epub 2007 Feb 6. Gastroenterology. 2007. PMID: 17408649 - Colonic vitamin D metabolism: implications for the pathogenesis of inflammatory bowel disease and colorectal cancer.
Cross HS, Nittke T, Kallay E. Cross HS, et al. Mol Cell Endocrinol. 2011 Dec 5;347(1-2):70-9. doi: 10.1016/j.mce.2011.07.022. Epub 2011 Jul 27. Mol Cell Endocrinol. 2011. PMID: 21801808 Review. - Intestinal calcium absorption: Molecular vitamin D mediated mechanisms.
Bouillon R, Van Cromphaut S, Carmeliet G. Bouillon R, et al. J Cell Biochem. 2003 Feb 1;88(2):332-9. doi: 10.1002/jcb.10360. J Cell Biochem. 2003. PMID: 12520535 Review.
Cited by
- Food components and the immune system: from tonic agents to allergens.
Faria AM, Gomes-Santos AC, Gonçalves JL, Moreira TG, Medeiros SR, Dourado LP, Cara DC. Faria AM, et al. Front Immunol. 2013 May 17;4:102. doi: 10.3389/fimmu.2013.00102. eCollection 2013. Front Immunol. 2013. PMID: 23730302 Free PMC article. - Supplementation of Vitamin D3 and Fructooligosaccharides Downregulates Intestinal Defensins and Reduces the Species Abundance of Romboutsia ilealis in C57BL/6J Mice.
Hanson T, Constantine E, Nobles Z, Butler E, Renteria KM, Teoh CM, Koh GY. Hanson T, et al. Nutrients. 2024 Jul 11;16(14):2236. doi: 10.3390/nu16142236. Nutrients. 2024. PMID: 39064679 Free PMC article. - The Role of Vitamin D Metabolism Genes and Their Genomic Background in Shaping Cyclosporine A Dosage Parameters after Kidney Transplantation.
Kotowska K, Wojciuk B, Sieńko J, Bogacz A, Stukan I, Drożdżal S, Czerny B, Tejchman K, Trybek G, Machaliński B, Kotowski M. Kotowska K, et al. J Clin Med. 2024 Aug 22;13(16):4966. doi: 10.3390/jcm13164966. J Clin Med. 2024. PMID: 39201108 Free PMC article. - Does Vitamin D Insufficiency Influence Prebiotic Effect on Calcium Absorption and Bone Retention?
Seijo M, Bonanno MN, Bryk G, Zeni Coronel ME, Pita Martin de Portela ML, Zeni SN. Seijo M, et al. Calcif Tissue Int. 2022 Sep;111(3):300-312. doi: 10.1007/s00223-022-00984-y. Epub 2022 May 3. Calcif Tissue Int. 2022. PMID: 35505249 - Sepsis and Acute Kidney Injury: A Review Focusing on the Bidirectional Interplay.
Chang YM, Chou YT, Kan WC, Shiao CC. Chang YM, et al. Int J Mol Sci. 2022 Aug 15;23(16):9159. doi: 10.3390/ijms23169159. Int J Mol Sci. 2022. PMID: 36012420 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases