ArticleKidney international2015
Excess 25-hydroxyvitamin D3 exacerbates tubulointerstitial injury in mice by modulating macrophage phenotype.
Article in Kidney international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Maxacalcitol (22-Oxacalcitriol (OCT)) Retards Progression of Left Ventricular Hypertrophy with Renal Dysfunction Through Inhibition of Calcineurin-NFAT Activity.Cardiovascular drugs and therapy · 2021Trial
- Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in Kidney Transplant Recipients: The FAVORIT Trial.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Trial
- Immune regulatory mechanisms of M2 macrophage polarization and efferocytosis in diabetic kidney disease: an integrated screening study with therapeutic implications.Frontiers in endocrinology · 2025Article
- Review
- Article
- Hepatic phosphate uptake and subsequent nerve-mediated phosphaturia are crucial for phosphate homeostasis following portal vein passage of phosphate in rats.Scientific reports · 2023Article
- The Role of Vitamin D in SARS-CoV-2 Infection and Acute Kidney Injury.International journal of molecular sciences · 2022Review
- Recurrent membranous nephropathy with a possible alteration in the etiology: a case report.BMC nephrology · 2021Article
- Quantitative Analyses of Foot Processes, Mitochondria, and Basement Membranes by Structured Illumination Microscopy Using Elastica-Masson- and Periodic-Acid-Schiff-Stained Kidney Sections.Kidney international reports · 2021Article
- Single cell RNA sequencing uncovers cellular developmental sequences and novel potential intercellular communications in embryonic kidney.Scientific reports · 2021Article
- Dietary casein, egg albumin, and branched-chain amino acids attenuate phosphate-induced renal tubulointerstitial injury in rats.Scientific reports · 2020Article
- Vitamin D's Effect on Immune Function.Nutrients · 2020Review
- Vitamin D and renal outcome: the fourth outcome of CKD-MBD? Oshima Award Address 2015.Clinical and experimental nephrology · 2018Article
- Review
- Vitamin D: can you have too much of a good thing in chronic kidney disease?Kidney international · 2015Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vitamin D hydroxylated at carbon 25 (25(OH)D) is generally recognized as a precursor of active vitamin D. Despite its low affinity for the vitamin D receptor (VDR), both deficient and excessive 25(OH)D levels are associated with poor clinical outcomes. Here we studied direct effects of 25(OH)D3 on the kidney using 25(OH)D-1α-hydroxylase (CYP27B1) knockout mice. The effects of 25(OH)D3 on unilateral ureteral obstruction were analyzed as proximal tubular cells and macrophages are two major cell types that take up 25(OH)D and contribute to the pathogenesis of kidney injury. Excess 25(OH)D3 in obstructed mice worsened oxidative stress and tubulointerstitial fibrosis, whereas moderate levels of 25(OH)D3 had no effects. The exacerbating effects of excess 25(OH)D3 were abolished in CYP27B1/VDR double-knockout mice and in macrophage-depleted CYP27B1 knockout mice. Excess 25(OH)D3 upregulated both M1 marker (TNF-α) and M2 marker (TGF-β1) levels of kidney-infiltrating macrophages. In vitro analyses verified that excess 25(OH)D3 directly upregulated TNF-α and TGF-β1 in cultured macrophages but not in tubular cells. TNF-α and 25(OH)D3 cooperatively induced oxidative stress by upregulating iNOS in tubular cells. Aggravated tubulointerstitial fibrosis in mice with excess 25(OH)D3 indicated that macrophage-derived TGF-β1 also had a key role in the pathogenesis of surplus 25(OH)D3. Thus, excess 25(OH)D3 worsens tubulointerstitial injury by modulating macrophage phenotype.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.