{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:29:51Z","timestamp":1793262591225,"version":"4.5.0"},"reference-count":37,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T00:00:00Z","timestamp":1700352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Fund of China","award":["81800470"],"award-info":[{"award-number":["81800470"]}]},{"name":"National Natural Science Fund of China","award":["82070544"],"award-info":[{"award-number":["82070544"]}]},{"name":"National Natural Science Fund of China","award":["2020YFS0239"],"award-info":[{"award-number":["2020YFS0239"]}]},{"name":"National Natural Science Fund of China","award":["2022YFS0173"],"award-info":[{"award-number":["2022YFS0173"]}]},{"name":"Sichuan Science and Technology Program","award":["81800470"],"award-info":[{"award-number":["81800470"]}]},{"name":"Sichuan Science and Technology Program","award":["82070544"],"award-info":[{"award-number":["82070544"]}]},{"name":"Sichuan Science and Technology Program","award":["2020YFS0239"],"award-info":[{"award-number":["2020YFS0239"]}]},{"name":"Sichuan Science and Technology Program","award":["2022YFS0173"],"award-info":[{"award-number":["2022YFS0173"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objectives: Vitamin D (VitD) and Vitamin D receptor (VDR) are suggested to play protective roles in the intestinal barrier in ulcerative colitis (UC). However, the underlying mechanisms remain elusive. Evidence demonstrates that Na+\/H+ exchanger isoform 8 (NHE8, SLC9A8) is essential in maintaining intestinal homeostasis, regarded as a promising target for UC therapy. Thus, this study aims to investigate the effects of VitD\/VDR on NHE8 in intestinal protection. Methods: VitD-deficient mice, VDR\u2212\/\u2212 mice and NHE8\u2212\/\u2212 mice were employed in this study. Colitis mice were established by supplementing DSS-containing water. Caco-2 cells and 3D-enteroids were used for in vitro studies. VDR siRNA (siVDR), VDR over-expression plasmid (pVDR), TNF-\u03b1 and NF-\u03bab p65 inhibitor QNZ were used for mechanical studies. The expression of interested proteins was detected by multiple techniques. Results: In colitis mice, paricalcitol upregulated NHE8 expression was accompanied by restoring colonic mucosal injury. In VitD-deficient and VDR\u2212\/\u2212 colitis mice, NHE8 expression was compromised with more serious mucosal damage. Noteworthily, paricalcitol could not prevent intestinal barrier dysfunction and histological destruction in NHE8\u2212\/\u2212 mice. In Caco-2 cells and enteroids, siVDR downregulated NHE8 expression, further promoted TNF-\u03b1-induced NHE8 downregulation and stimulated TNF-\u03b1-induced NF-\u03bab p65 phosphorylation. Conversely, QNZ blocked TNF-\u03b1-induced NHE8 downregulation in the absence or presence of siVDR. Conclusions: Our study indicates depressed NHE8 expression is responsible for VitD-deficient-induced colitis aggravation. These findings provide novel insights into the molecular mechanisms of VitD\/VDR in intestine protection in UC.<\/jats:p>","DOI":"10.3390\/nu15224834","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:30:50Z","timestamp":1700440250000},"page":"4834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Compromised NHE8 Expression Is Responsible for Vitamin D-Deficiency Induced Intestinal Barrier Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"given":"Yaoyu","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanni","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeya","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Outpatient, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Geng","sequence":"additional","affiliation":[{"name":"Laboratory of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuailing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S2468-1253(19)30173-6","article-title":"Comorbidities in inflammatory bowel disease: A call for action","volume":"4","author":"Argollo","year":"2019","journal-title":"Lancet Gastroenterol. 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