Vitamin D strengthens the bladder epithelial barrier by inducing tight junction proteins during E. coli urinary tract infection

Abstract

Tight junction proteins are pivotal to prevent bacterial invasion of the epithelial barrier. We here report that supplementation with vitamin D can strengthen the urinary bladder lining. Vitamin D deficient and sufficient mice were infected with Escherichia coli (E. coli) transurethrally to cause urinary tract infection. In addition, bladder biopsies were obtained from postmenopausal women before and after a 3-month period of supplementation with 25-hydroxyvitamin D3 (25D3) and ex vivo infected with E. coli. In biopsies, obtained before E. coli infection, vitamin D had no impact on tight junction proteins. However, during E. coli infection, vitamin D induced occludin and claudin-14 in mature superficial umbrella cells of the urinary bladder, as demonstrated by immunohistochemistry. Increased cell-cell adhesion consolidating the epithelial integrity is thereby promoted. We here describe a novel role of vitamin D in the urinary tract supporting vitamin D supplementation to restore the bladder epithelial integrity.

1α,25(OH) 2 D 3 (VD3) promotes Raddeanin A-induced anti-proliferative effects on HeLa cell apoptosis and autophagy through negative regulation of HPV18E6-E7/PD-L1/VDR axis

“…Serum VD3 can regulate host immunity through involvement in the regulation of antimicrobial peptides (AMPs) production, a nonspecific innate defense, which has been suggested as the mechanism of protection for many infections [ 44 ]. Moreover, sufficient vitamin D makes the physical barriers of skin and mucosa more resistant to HPV via elevating proteins that promote tight junctions, gap junctions, and adherens junctions [ 45 ], conversely, insufficient vitamin D may generate a higher prevalence of HPV infection by increasing HPV penetration and reducing the host immunity, which lead to HPV persistence and cervical epithelial neoplasia [ 46 , 47 ], as well as the poor prognosis of gynecological tumors. Furthermore, the expression of VDR increases in tumor tissues including cervical and ovarian cancer, and multiple VDR polymorphisms, especially FokI and BsmI VDR gene polymorphisms, inhibits the activity of vitamin D, which leads to development of gynecological cancers [ 48 ].…”

Vitamin D Receptor Influences Intestinal Barriers in Health and Disease

“…Vitamin D upregulates TJ proteins occludin and claudin-14 during E. coli urinary tract infection [ 73 ], likely improving the epithelial integrity, which in turn may ameliorate the protection against infection. This finding is relevant especially among patients with recurrent urinary tract infection (UTI) and where low vitamin D levels are anticipated.…”

Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy

“…Dust mite-induced rhinitis induces barrier leak in human nasal epithelial cell layers, a condition partially countered by Vitamin D [ 246 ]. Mouse urinary bladder epithelial barriers compromised by E. coli infection were partially protected by Vitamin D administration, reversing the infection-induced reduction in occludin and claudin-14 [ 374 ]. Partial VDR knockout in mice resulted in a more severely, LPS-compromised pulmonary epithelial barrier, with decreased occludin and ZO-1 expression, and this situation was alleviated by Vitamin D [ 375 ].…”