{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:09:20Z","timestamp":1789150160361,"version":"build-2803163510"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KOREAN NEPHROLOGY RESEARCH FOUNDATION","award":["Young Investigator Research Grant"],"award-info":[{"award-number":["Young Investigator Research Grant"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2020R1A5A2019210"],"award-info":[{"award-number":["2020R1A5A2019210"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD) and promotes oxidative stress, endothelial dysfunction, vascular smooth muscle cell proliferation, and fibrosis, thereby contributing to vascular stenosis in patients receiving hemodialysis. CKD is also commonly associated with vitamin D deficiency, which is linked to vascular calcification, immune dysregulation, and inflammation. This study aims to investigate the preventive effects of 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    (active vitamin D) against IS-induced macrophage inflammatory activation and cholesterol dysregulation. Macrophages were pretreated with 30 nM 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    for 12 and 24 h, followed by exposure to IS at concentrations of 125 and 250 \u00b5g\/mL for 24 h. Morphological changes were observed under a microscope. To assess macrophage phenotype-associated changes, qPCR was performed to analyze the expression of M1-like\/pro-inflammatory markers (TNF-\u03b1 and IL-1\u03b2) and M2-like\/anti-inflammatory phenotype-associated markers (CD163 TGF-\u03b2 and IL-10). Cholesterol metabolism was assessed using a cholesterol efflux assay, qPCR analysis of ABCA1 and ABCG1 and Oil Red O staining for intracellular lipid accumulation. Protein expression of inflammatory mediators, TGF-\u03b21, and cholesterol efflux transporters was further evaluated by western blotting. 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    pretreatment modulated IS-associated inflammatory responses, as reflected by changes in selected M1-like\/pro-inflammatory mediators, including iNOS, IL-6 and IL-1\u03b2. Conversely, 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    increased selected M2-like\/anti-inflammatory phenotype-associated markers, including CD163 and IL-10. Furthermore, 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    pretreatment preserved cholesterol efflux capacity and modulated ABCA1 and ABCG1 expression in a time- and transporter-dependent manner, accompanied by reduced intracellular lipid accumulation as shown by Oil red O staining. These findings suggest that 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    may protect macrophages against IS-induced inflammatory activation and cholesterol dysregulation, highlighting its potential as a preventive or modulatory approach for macrophage-mediated vascular dysfunction in CKD.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0357984","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:32:12Z","timestamp":1789147932000},"page":"e0357984","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vitamin D alleviates indoxyl sulfate-induced inflammatory and cholesterol dysregulation in macrophages: Implications for vascular health in patients receiving hemodialysis"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0223-5095","authenticated-orcid":true,"given":"Kyoung Hye","family":"Kong","sequence":"first","affiliation":[{"name":"Ewha Womans University College of Medicine","place":["Seoul, Republic of Korea"],"department":["Ewha Medical Research Center"]},{"name":"Ewha Womans University College of Medicine","place":["Seoul, Republic of Korea"],"department":["Inflammation-Cancer Microenvironment Research Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungwon","family":"Yang","sequence":"additional","affiliation":[{"name":"Ewha Womans University College of Medicine","place":["Seoul, Republic of Korea"],"department":["Ewha Medical Research Center"]},{"name":"Ewha Womans University College of Medicine","place":["Seoul, Republic of Korea"],"department":["Inflammation-Cancer Microenvironment Research Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1648-624X","authenticated-orcid":true,"given":"Jung-Hwa","family":"Ryu","sequence":"additional","affiliation":[{"name":"Ewha Womans University College of Medicine","place":["Seoul, Republic of Korea"],"department":["Inflammation-Cancer Microenvironment Research Center"]},{"name":"Ewha Womans University College of Medicine","place":["Seoul, Republic of Korea"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"issue":"2","key":"pone.0357984.ref001","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3390\/toxins13020142","article-title":"Uremic toxins in the progression of chronic kidney disease and cardiovascular disease: mechanisms and therapeutic targets","volume":"13","author":"YJ Lim","year":"2021","journal-title":"Toxins 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