1,25-Dihydroxyvitamin D and Klotho

Haussler, Mark R.; Whitfield, G. Kerr; Haussler, Carol A.; Sabir, Marya S.; Khan, Zainab; Sandoval, Ruby; Jurutka, Peter W.

doi:10.1016/bs.vh.2015.11.005

Cited by 49 publications

(21 citation statements)

References 253 publications

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“…Vitamin D plays a role in preventing anemia but also decreases oxidative stress, insulin resistance, and inflammation [23,24,47]. Ferritin is a marker of iron deficiency anemia but may also be a marker of oxidative stress, insulin resistance, and inflammation [37,48].…”

Section: Discussionmentioning

confidence: 99%

Gender difference in relationship between serum ferritin and 25-hydroxyvitamin D in Korean adults

et al. 2017

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BackgroundThe present study was conducted to assess the gender difference in the relationship between serum ferritin and 25-hydroxyvitamin D [25(OH)D] in Korean adults.MethodsA total of 5,147 adults (2,162 men, 1,563 premenopausal women, and 1,422 postmenopausal women) aged ≥ 20 years from the Korean National Health and Nutrition Examination Survey (KNHANES) data (2012) were analyzed. A covariance test adjusted for covariates was performed for serum ferritin levels in relation to vitamin D status (vitamin D deficiency, 25(OH)D < 10.0 ng/mL; vitamin D insufficiency, 25(OH)D ≥ 10.0, < 20.0 ng/mL; vitamin D sufficiency, 25(OH)D ≥ 20.0 ng/mL).ResultsThe key study results were as follows: First, in men, in terms of serum ferritin levels by serum 25(OH)D level after adjusting for age, smoking, alcohol drinking, regular exercise, SBP, DBP, WM. TC, TGs, HDL-C, FPG, Hb, Hct, MCV, and Fe, serum ferritin levels were inversely increased with the increasing of serum 25(OH)D level (P = 0.012). Second, in premenopausal women, after adjusting for related variables, serum ferritin levels were increased with the increasing of serum 25(OH)D level (P = 0.003). Third, in postmenopausal women, after adjusting for related variables, serum ferritin levels were not significantly increased with the increasing of serum 25(OH)D level (P = 0.456).ConclusionSerum 25(OH)D level was inversely associated with the serum ferritin levels in men, but was positively associated with the serum ferritin levels in premenopausal women, and was not associated with the serum ferritin levels in postmenopausal women.

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Section: Discussionmentioning

confidence: 99%

Gender difference in relationship between serum ferritin and 25-hydroxyvitamin D in Korean adults

et al. 2017

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“…VDR is additionally activated by vitamin D 3 metabolites and synthetic analogs, but is insensitive to other steroid hormones, vitamins, primary bile acids, and xenobiotics [15,22,23]. The canonical role of VDR is in regulating calcium homeostasis and skeletal maintenance, however additional non-calcemic functions have been identified, including roles in cell proliferation and differentiation, immune response, and neurodevelopment [24]. Like most NRs, VDR activation is initiated by ligand binding, which triggers a conformational change in the receptor and stimulates a strong association between VDR and the retinoid X receptor (RXR).…”

Section: Introductionmentioning

confidence: 99%

Evolutionary and Functional Diversification of the Vitamin D Receptor-Lithocholic Acid Partnership

et al. 2016

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The evolution, molecular behavior, and physiological function of nuclear receptors are of particular interest given their diverse roles in regulating essential biological processes. The vitamin D receptor (VDR) is well known for its canonical roles in calcium homeostasis and skeletal maintenance. Additionally, VDR has received an increased amount of attention due to the discovery of numerous non-calcemic functions, including the detoxification of lithocholic acid. Lithocholic acid is a toxic metabolite of chenodeoxycholic acid, a primary bile acid. The partnership between the VDR and lithocholic acid has been hypothesized to be a recent adaptation that evolved to mediate the detoxification and elimination of lithocholic acid from the gut. This partnership is speculated to be limited to higher vertebrates (birds and mammals), as lower vertebrates do not synthesize the parent compound of lithocholic acid. However, the molecular functions associated with the observed insensitivity of basal VDRs to lithocholic acid have not been explored. Here we characterize canonical nuclear receptor functions of VDRs from select species representing key nodes in vertebrate evolution and span a range of bile salt phenotypes. Competitive ligand binding assays revealed that the receptor’s affinity for lithocholic acid is highly conserved across species, suggesting that lithocholic acid affinity is an ancient and non-adaptive trait. However, transient transactivation assays revealed that lithocholic acid-mediated VDR activation might have evolved more recently, as the non-mammalian receptors did not respond to lithocholic acid unless exogenous coactivator proteins were co-expressed. Subsequent functional assays indicated that differential lithocholic acid-mediated receptor activation is potentially driven by differential protein-protein interactions between VDR and nuclear receptor coregulator proteins. We hypothesize that the vitamin D receptor-lithocholic acid partnership evolved as a by-product of natural selection on the ligand-receptor partnership between the vitamin D receptor and the native VDR ligand: 1α,25-dihydroxyvitamin D3, the biologically active metabolite of vitamin D3.

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“…Even though the main function of the kidney is to excrete waste products from the bloodstream, it is important to mention that the kidney is also a major endocrine organ. Five very important hormones/enzymes are produced by the kidney, viz, 1,25-dihydroxyvitamin D3, erythropoietin, renin, Klotho, and kallikrein (Haussler et al 2016); (Shimamoto and Iimura 1989). Calcitriol, 1,25-dihydroxyvitamin D3, is activated in the proximal tubule and acts in the reabsorption of calcium, but it is also involved in bone health and in the regulation of parathyroid function (Kumar et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Kidney-based in vitro models for drug-induced toxicity testing

et al. 2019

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The kidney is frequently involved in adverse effects caused by exposure to foreign compounds, including drugs. An early prediction of those effects is crucial for allowing novel, safe drugs entering the market. Yet, in current pharmacotherapy, drug-induced nephrotoxicity accounts for up to 25% of the reported serious adverse effects, of which one-third is attributed to antimicrobials use. Adverse drug effects can be due to direct toxicity, for instance as a result of kidney-specific determinants, or indirectly by, e.g., vascular effects or crystals deposition. Currently used in vitro assays do not adequately predict in vivo observed effects, predominantly due to an inadequate preservation of the organs' microenvironment in the models applied. The kidney is highly complex, composed of a filter unit and a tubular segment, together containing over 20 different cell types. The tubular epithelium is highly polarized, and the maintenance of this polarity is critical for optimal functioning and response to environmental signals. Cell polarity is dependent on communication between cells, which includes paracrine and autocrine signals, as well as biomechanic and chemotactic processes. These processes all influence kidney cell proliferation, migration, and differentiation. For drug disposition studies, this microenvironment is essential for prediction of toxic responses. This review provides an overview of drug-induced injuries to the kidney, details on relevant and translational biomarkers, and advances in 3D cultures of human renal cells, including organoids and kidney-on-a-chip platforms.

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1,25-Dihydroxyvitamin D and Klotho

Cited by 49 publications

References 253 publications

Gender difference in relationship between serum ferritin and 25-hydroxyvitamin D in Korean adults

Gender difference in relationship between serum ferritin and 25-hydroxyvitamin D in Korean adults

Evolutionary and Functional Diversification of the Vitamin D Receptor-Lithocholic Acid Partnership

Kidney-based in vitro models for drug-induced toxicity testing

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