Therefore, vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD. VDR knockdown with small interfering (si)RNA reduced the junction proteins and TER in Caco-2 monolayers. Choroid plexus epithelial cells express high levels of folate receptor a (FRa) suggesting that the choroid plays an impor-tant role in CNS folate trafficking and maintenance of CSF folate levels. 5, Journal of Animal Science, Vol. Immunohistochemical expression of VDR is associated with reduced integrity of tight junction complex in psoriatic skin, Vitamin D receptor pathway is required for probiotic protection in colitis, Protective effect of 1,25-dihydroxyvitamin D3 on ethanol-induced intestinal barrier injury both in vitro and in vivo, Tight junction CLDN2 gene is a direct target of the vitamin D receptor, Regulation of Dendritic Cell Function by Vitamin D, Breast Milk and Solid Food Shaping Intestinal Immunity, Immune Modulation by Vitamin D and Its Relevance to Food Allergy, Transgenic Expression of Vitamin D Receptor in Gut Epithelial Cells Ameliorates Spontaneous Colitis Caused by Interleukin-10 Deficiency, Does Vitamin D Protect the Gut Mucosal Barrier? Vitamins are organic compounds your body needs to perform all of its essential functions - like growing tissues, regulating metabolism and maintaining a healthy immune system. 110, No. 2.Effect of DSS on colonic transepithelial electric resistance (TER). As in the case of SW480 cells, 1,25(OH)2D3 induced ZO-1 and E-cadherin in Caco-2 cells (Fig. 309, No. Vitamin A plays a significant role in vision, bone growth, reproduction, cell division and cell differentiation. 3, 6 September 2013 | Hepatology, Vol. 130, 1 August 2018 | Expert Review of Gastroenterology & Hepatology, Vol. Cathelicidin plays a protective role in 25(OH)D-associated UC histologic outcomes and murine colitis. The identification of dehydroretinol (vitamin A2) in human skin. Vitamin D Deficiency Predisposes to Adherent-invasive Escherichia coli-induced Barrier Dysfunction and Experimental Colonic Injury, Cytochrome P450 Vitamin D Hydroxylases in Inflammation and Cancer, Mucosal Healing in Inflammatory Bowel Diseases, Cloning of a functional 25-hydroxyvitamin D-1α-hydroxylase in zebrafish ( 12, No. 60, No. 361, 9 April 2014 | Molecular Medicine Reports, Vol. We have characterized 5-methyltetrahydrofolate (5-MTHF) uptake and metabolism by primary rat choroid plexus epithelial cells in vitro. 1, No. 2, The American Journal of Pathology, Vol. Therefore, the VDR appears to be required for mucosal repair. 15, Revue Française d'Allergologie, Vol. 10, 29 July 2015 | Alimentary Pharmacology & Therapeutics, Vol. PCR amplification was carried out using specific primers designed based on cDNA sequences deposited in the GenBank database (Table 1). 12, 7 October 2016 | BMC Gastroenterology, Vol. Therefore, vitamin D may participate in preservation of the junctions by increasing the level of some key junction proteins. a and b: Hematoxylin and eosin (H and E) staining of “Swiss rolls” of the entire large intestine on day 7. 94, 95 Locally activated vitamin D can directly induce the expression of cathelicidin peptides. 7, 19 May 2015 | Digestive Diseases and Sciences, Vol. 3A, c and g; 3B, a and b). 8A). 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. B: colon from DSS-treated VDR+/+ mice on day 15. -induced intestine epithelial autophagy and interleukin-1β expression, Nutritional Keys for Intestinal Barrier Modulation, Impact of the birth’s season on the development of celiac disease in Italy, The Gut-Brain Axis: The Role of the Gut in Brain Health, Dietary vitamin D3 deficiency alters intestinal mucosal defense and increases susceptibility to Citrobacter rodentium-induced colitis, 1,25-Dihydroxyvitamin D Protects Intestinal Epithelial Barrier by Regulating the Myosin Light Chain Kinase Signaling Pathway, Association Between Inflammatory Bowel Disease and Vitamin D Deficiency, Association of Vitamin D Status and Clinical Outcome in Dogs with a Chronic Enteropathy, Temporal plasma vitamin concentrations are altered by fat-soluble vitamin administration in suckling pigs1, Vitamin D Deficiency Associated with Disease Activity in Patients with Inflammatory Bowel Diseases. We compared colitis development in VDR+/+ and VDR−/− mice treated with DSS. Address for reprint requests and other correspondence: Yan Chun Li, Dept. A. 26, No. 19, No. Note the disruption of the tight junctions and desmosomes in the VDR−/− mucosal epithelia (B). Taken together, these findings reveal a fundamental role for Vitamin A in the development of both regulatory and inflammatory arms of immune responses and establish nutritional status as a … 1-2, Pharmacogenetics and Genomics, Vol. It also helps form red blood cells and maintain the central nervous system. In summary, in this report we presented evidence suggesting that the VDR plays a critical role in preserving the integrity of the intestinal mucosal barrier. 39, No. 1, Journal of Crohn's and Colitis, Vol. 4, Current Opinion in Clinical Nutrition and Metabolic Care, Vol. 9, No. Epidemiological evidence has suggested an association between vitamin D deficiency and increased IBD risk (23); however, the underlying mechanisms remain to be elucidated. Cell 7(84):1–28 Margaret PR (2000) The importance of selenium to human health. 46, No. 10, Journal of Clinical Investigation, Vol. One exception is occludin, which is not directly regulated by vitamin D in cell culture but diminished from VDR−/− colonic mucosa under DSS insult. 1981;270(2):193-6. doi: 10.1007/BF00408234. 3, No. Of note is an early study that reported reduction of TER by 1,25(OH)2D3 in Caco-2 monolayers (2). C: survival curve. 3, 13 September 2016 | Cellular and Molecular Life Sciences, Vol. 1, 8 June 2016 | The American Journal of Clinical Nutrition, Vol. Caco-2 cells form tight junctions when grown to monolayers on membrane filters. 2, Inflammatory Bowel Diseases, Vol. 42, No. 11:1160. doi: 10.3389/fimmu.2020.01160. 11, 2 June 2015 | Digestive Diseases and Sciences, Vol. After death, the colons were harvested, fixed in 10% formalin (pH 7.4), processed, and paraffin embedded. 8, No. By Milos Mihajlovic, Michele Fedecostante, Miriam J Oost, Sonja K P Steenhuis, Eef G W M Lentjes, Inge Maitimu-Smeele, Manoe J Janssen, Luuk B Hilbrands and Rosalinde Masereeuw. 254, No. Seasonal variations in the onset and exacerbation of IBD have also been reported (27, 36) with high incidence in the winter. 303, No. 1, The Journal of Steroid Biochemistry and Molecular Biology, Vol. The most critical role that vitamin A plays in the human body is _____. The slides were stained with anti-VDR antibody (Santa Cruz) or anti-BrdU monoclonal antibody (Roche). 6.Effect of vitamin D on tight junctions. This article discusses vitamin A, including its benefits, food sources, as well as effects of deficiency and toxicity. Vitamin A is a fat-soluble nutrient that plays a vital role in your body. The tissues were dehydrated in an ascending series of ethanol, infiltrated with Eponate 12 resin (Ted Pella, Redding, CA) and then embedded and polymerized at 70°C for 24 h. Resin-embedded blocks were sectioned at 70 nm and collected on 200-mesh, Formvar-coated copper grids. 1D, e). DSS has been shown to increase mucosal permeability in mice (14). 7, 1 July 2013 | American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 57, No. 3, Journal of Allergy and Clinical Immunology, Vol. 22, No. As shown in Fig. 72, No. 11, 1 October 2012 | American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 6, Research in Veterinary Science, Vol. 36, No. Retinol is obtained from foods of animal origin. 3, 11 February 2015 | United European Gastroenterology Journal, Vol. Data were presented as means ± SD. 148, 26 October 2014 | Inflammation, Vol. 1, World Journal of Gastroenterology, Vol. These junctions seal the paracellular space and regulate the permeability of the mucosal barrier. 2, 27 November 2010 | Clinical Rheumatology, Vol. The biochemical and physiological role of vitamins A and E and their interactions. 7, 21 June 2014 | Hepatology International, Vol. According to the U.S. National Library of Medicine, the best way to meet your vitamin needs is to eat a balanced diet containing a variety of foods. 1, Current Opinion in Gastroenterology, Vol. 20, 3 May 2018 | Journal of Crohn's and Colitis, Vol. The biological role of vitamin A in maintaining epithelial tissues. 1D, a–d), and 10 (Fig. 21, No. 21, No. Arch Dermatol Res. 2, 21 April 2010 | Journal of Cellular Biochemistry, Vol. 1830, No. 4, Current Opinion in Gastroenterology, Vol. 3.Effect of DSS on colonic epithelial junctions. Magnification: ×200. This observation suggests that vitamin D may stimulate epithelial restitution in mucosal wound healing. Animal studies using IL-10 knockout mice have pointed to an immunomodulating role of VDR in IBD development. Histological examination revealed extensive ulceration and impaired wound healing in the colonic epithelium of DSS-treated VDR−/− mice. 3, No. *P < 0.05 vs. VDR+/+, n = 3 or 4 of each genotype. As a promotor for Figure 1. 13, No. 6, 16 February 2018 | Inflammatory Bowel Diseases, Vol. To knockdown VDR, Caco-2 cells were transfected with human (h)VDR-small interfering (si)RNA and scramble siRNA using Transfectamine 2000 (Invitrogen). 14, No. 3, No. Previous studies have suggested a link between vitamin D deficiency and IBD risk (23). C, D, and E: effect of vitamin D on tight junctions formed by Caco-2 cells. Using this model, we found that mice lacking VDR are much more susceptible to mucosal injury than wild-type mice. Although the exact action of DSS is not fully understood, it is believed that DSS causes mucosal injury and disrupts the barrier function, leading to inflammation. 6, 23 February 2017 | Allergy, Vol. More in-depth investigations are required to elucidate the VDR-regulated downstream events involved in mucosal repair. Effect of squamous metaplasia on infection of hamster trachea organ cultures with Mycoplasma pneumoniae. The size of the VDR−/− cells is increased due to cell swell. Vitamin A is a fat-soluble nutrient that plays a vital role in your body. Grids were stained with uranyl acetate and lead citrate and examined with a JEOL 1200 EX II transmission electron microscope. DSS has been shown to increase mucosal permeability in mice (14) and reduce TER in intestinal cell monolayers (39), and the DSS-colitis model has been widely used to study mucosal healing (20, 25, 41). 10, Journal of Crohn's and Colitis, Vol. 1, 19 January 2017 | Innate Immunity, Vol. In cell cultures, 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] 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. 523, No. 7, 14 June 2018 | JNCI: Journal of the National Cancer Institute, Vol. Urinary Stones Urinary calculi, or solid particles in the urinary system, may cause pain, nausea and vomiting when stones are formed. No signs of healing and reepithelization or crypt formation were seen over the broad ulcer area in VDR−/− mice (f). 1C). Which of the following factors can explain why vitamin D deficiency is on the rise? Two- to 3-mo-old mice were fed 2% or 2.5% dextran sodium sulfate (DSS) dissolved in drinking water for indicated days, and the mice were either killed or fed regular water and killed at a later time point. 22, No. 1, Journal of the American Heart Association, Vol. *P < 0.05 vs. VDR+/+. 28, No. VDR+/+ (wild-type) and VDR−/− mice in C57BL6 background were obtained by breeding VDR+/− mice (22). This process involves several signaling molecules such as growth factors, hormones and vitamins. 2 40, No. 1, 29 May 2014 | Clinical and Translational Gastroenterology, Vol. B: VDR protein levels were monitored by Western blot analysis at 4, 7, and 9 days after hVDR-siRNA transfection. Indeed, in VDR+/+ mice, after DSS treatment was stopped, epithelial restitution, proliferation, and new crypt formation were clearly seen in the ulcerated lesions. Aspartame inhibits migration of human intestinal epithelial cells, Leaky Gut As a Danger Signal for Autoimmune Diseases, Mucosal Ecological Network of Epithelium and Immune Cells for Gut Homeostasis and Tissue Healing, Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals, The effect of polymeric formula on enterocyte differentiation, Molecular pathways driving disease-specific alterations of intestinal epithelial cells, Computational methods using genome-wide association studies to predict radiotherapy complications and to identify correlative molecular processes, The Role of Interleukin-1 in Inflammatory and Malignant Human Skin Diseases and the Rationale for Targeting Interleukin-1 Alpha, Vitamin D receptor is a novel transcriptional regulator for Axin1, ASTHMA – comparing the impact of vitamin D versus UVR on clinical and immune parameters, Diet as a Trigger or Therapy for Inflammatory Bowel Diseases, Nutrition and IBD: Malnutrition and/or Sarcopenia? https://orcid.org. 1.Vitamin D receptor (VDR)−/− mice develop more severe dextran sodium sulfate (DSS)-induced colitis than VDR+/+ mice. 239, No. The reason for the discrepancy between that study and our present study is unknown. 12, 13 November 2013 | Gastroenterology Report, Vol. (a) maintaining a healthy reproductive system. Nutr Rev. 5A). Early studies have reported a high prevalence of vitamin D deficiency in patients with established Crohn's disease (12, 38). 1980 Mar 15;36(3):317-8. doi: 10.1007/BF01952299. Atopic Dermatitis: A Disease Caused by Innate Immune Defects? The progeny of the dividing cells migrate upwards from the base to the luminal surface of the crypt (34). 1, 1 January 2009 | International Journal of Immunopathology and Pharmacology, Vol. Vitamins and minerals play an important role on people’s health. 40, No. When Caco-2 monolayers were incubated with 5% DSS, the TER gradually decreased over the following 3.5 h in the control cells; in contrast, in 1,25(OH)2D3-treated cells, the TER was moderately reduced in the beginning and fully recovered by 3.5 h (Fig. On the pathophysiology of vitamin A deficiency. 189, No. It is one of the eight B vitamins. 3, 30 March 2017 | Oral Diseases, Vol. They also play important roles in bodily functions such as metabolism, immunity and digestion. The clinical symptoms included diarrhea, gross bleeding, and rectal prolapse. The observation that VDR knockdown by siRNA led to downregulation of junction proteins and loss of TER confirms the importance of VDR-mediated vitamin D signaling in tight junction regulation. After 24-h starvation in serum-free media, the monolayers were scratched with a sterile razor blade. 6, 5 July 2015 | European Journal of Pediatrics, Vol. The TER is presented as % of the basal value in cells at 0 min not treated with DSS. Confocal and electron microscopy (EM) revealed severe disruption in epithelial junctions in VDR−/− mice after 3-day DSS treatment. The TER in each colonic segment was measured using the Ussing chamber. Vitamin D, sometimes called the ‘sunshine vitamin’ is a fat-soluble vitamin obtained from food and made by the body when sunlight hits the skin. 4, 10 July 2012 | Seminars in Immunopathology, Vol. 60, No. D: histological assessment of colonic mucosa of VDR+/+ (a, c, and e) and VDR−/− (b, d, and f) mice. 3, 23 May 2017 | Frontiers in Immunology, Vol. A P value of 0.05 or smaller was considered statistically significance. Good sources of B12. Study indicates vitamin A plays key role in the human body.  |  6, Journal of Animal Science, Vol. First-strand cDNA templates were synthesized using Moloney murine leukemia virus (MML-V) reverse transcriptase (Invitrogen) and hexanucleotide random primers. 1, 12 June 2012 | Alimentary Pharmacology & Therapeutics, Vol. 3, 11 July 2012 | Cellular and Molecular Life Sciences, Vol. Vitamin A (VitA) is a micronutrient that is crucial for maintaining vision, promoting growth and development, and protecting epithelium and mucus integrity in the body. However, the role of vitamin D and/or VDR in the regulation of intestinal barrier integrity has hardly been studied. The DSS-colitis model shares many clinical and pathological features of human ulcerative colitis with regard to ulceration and loss of barrier function (28). Niacin (vitamin B3; nicotinic acid) plays an important role in maintaining redox state of cells, and is obtained from endogenous and exogenous sources. This vitamin also plays an important role in the proteins that are part of many chemical reactions in the body. A: body weight (BW) curve. Body weight and animal symptoms, including the extent of diarrhea and rectal bleeding, were closely monitored during and after DSS treatment. One reason that fat-soluble vitamins are grouped together is because they: a. provide similar functions in the body. The intestinal stem cells, located at the base of the crypt, are responsible for replenishing the epithelium through cell division and differentiation. Regarding immunity, vitamin A contributes to supporting the integrity of epithelia, particularly About Europe PMC; Preprints in Europe … 4, 7 January 2012 | Current Colorectal Cancer Reports, Vol. 1D, e and f) after 2.5% DSS treatment. 1778, No. 92, No. 39, World Journal of Gastroenterology, Vol. Matsumoto Y(1), Nakanishi Y(2), Yoshioka T(1), Yamaga Y(1), Masuda T(1), Fukunaga Y(3)(4), Sono M(1), Yoshikawa T(1), Nagao M(1), Araki O(1), Ogawa S(1), Goto N(1), Hiramatsu Y(1), Breyer RM(5), Fukuda A(1), Seno H(1). The most critical role that vitamin A plays in the human body is _____. 1, 21 January 2016 | Graefe's Archive for Clinical and Experimental Ophthalmology, Vol. In the subapical adherens junction, the neighboring cell membranes are adhered by cadherins. 110, No. 1, Inflammatory Bowel Diseases, Vol. 5, No. Experientia. B: VDR−/− mice develop more severe clinical symptoms, reflected by higher symptom scores on days 3 and 7. Europe PMC. 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