Lithocholic acid increases intestinal phosphate and calcium absorption in a vitamin D receptor dependent but transcellular pathway independent manner

Hashimoto, Nozomi; Matsui, Isao; Ishizuka, Satoshi; Inoue, Kazunori; Matsumoto, Ayumi; Shimada, Kazuaki; Hori, Shigeaki; Lee, Dong Geun; Yasuda, Seiichi; Katsuma, Yusuke; Kajimoto, Shinji; Doi, Yasufumi; Yamaguchi, Satoshi; Kubota, Keiichi; Oka, Tetsushi; Sakaguchi, Yusuke; Takabatake, Yoshitsugu; Hamano, Takayuki; Isaka, Yoshitaka

doi:10.1016/j.kint.2020.01.032

Cited by 38 publications

(45 citation statements)

References 49 publications

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“…It has been recently reported that lithocholic acid increases intestinal P i absorption in a way that is Vdr dependent but independent of Na + ions and NaPi‐IIb, and it was suggested that the effect was mediated by an increase in paracellular permeability (Hashimoto et al . 2020). The well‐known effect of 1,25(OH) 2 vitamin D 3 on NaPi‐IIb abundance and intestinal Na + /P i transport (Hattenhauer et al .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the increase in intestinal absorption of P i (and Ca 2+ ) induced by lithocholic acid was reported to require the Vdr but to be independent of NaPi‐IIb (Hashimoto et al . 2020). Therefore, the aim of this study was to investigate whether NaPi‐IIb is solely responsible for the increased intestinal absorption of P i induced by 1,25(OH) 2 vitamin D 3 or whether paracellular P i absorption is also regulated.…”

Section: Introductionmentioning

confidence: 99%

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1,25(OH)₂ vitamin D₃ stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

Hernando

Pastor-Arroyo

Marks

et al. 2020

The Journal of Physiology

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Key points Intestinal absorption of phosphate proceeds via an active/transcellular route mostly mediated by NaPi‐IIb/Slc34a2 and a poorly characterized passive/paracellular pathway. Intestinal phosphate absorption and expression of NaPi‐IIb are stimulated by 1,25(OH)2 vitamin D3 but whether NaPi‐IIb is the only target under hormonal control remains unknown. We report that administration of 1,25(OH)2 vitamin D3 to wild‐type mice resulted in the expected increase in active transport of phosphate in jejunum, without changing paracellular fluxes. Instead, the same treatment failed to alter phosphate transport in intestinal‐depleted Slc34a2‐deficient mice. In both genotypes, 1,25(OH)2 vitamin D3 induced similar hyperphosphaturic responses and changes in the plasma levels of FGF23 and PTH. While urinary phosphate loss induced by administration of 1,25(OH)2 vitamin D3 did not alter plasma phosphate, further studies should investigate whether chronic administration would lead to phosphate imbalance in mice with reduced active intestinal absorption. Abstract Intestinal absorption of phosphate is stimulated by 1,25(OH)2 vitamin D3. At least two distinct mechanisms underlie phosphate absorption in the gut, an active transcellular transport requiring the Na+/phosphate cotransporter NaPi‐IIb/Slc34a2, and a poorly characterized paracellular passive pathway. 1,25(OH)2 vitamin D3 stimulates NaPi‐IIb expression and function, and loss of NaPi‐IIb reduces intestinal phosphate absorption. However, it is remains unknown whether NaPi‐IIb is the only target for hormonal regulation by 1,25(OH)2 vitamin D3. Here we compared the effects of intraperitoneal administration of 1,25(OH)2 vitamin D3 (2 days, once per day) in wild‐type and intestinal‐specific Slc34a2‐deficient mice, and analysed trans‐ vs. paracellular routes of phosphate absorption. We found that treatment stimulated active transport of phosphate only in jejunum of wild‐type mice, though NaPi‐IIb protein expression was upregulated in jejunum and ileum. In contrast, 1,25(OH)2 vitamin D3 administration had no effect in Slc34a2‐deficient mice, suggesting that the hormone specifically regulates NaPi‐IIb expression. In both groups, 1,25(OH)2 vitamin D3 elicited the expected increase of plasma fibroblast growth factor 23 (FGF23) and reduction of parathyroid hormone (PTH). Treatment resulted in hyperphosphaturia (and hypercalciuria) in both genotypes, though mice remained normophosphataemic. While increased intestinal absorption and higher FGF23 can trigger the hyperphosphaturic response in wild types, only higher FGF23 can explain the renal response in Slc34a2‐deficient mice. Thus, 1,25(OH)2 vitamin D3 stimulates intestinal phosphate absorption by acting on the active transcellular pathway mostly mediated by NaPi‐IIb while the paracellular pathway appears not to be affected.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

1,25(OH)₂ vitamin D₃ stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

Hernando

Pastor-Arroyo

Marks

et al. 2020

The Journal of Physiology

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“…Antibodies against the following molecules were used: myoshin-11 (ab53219, Abcam, Cambridge, UK), α-smooth muscle actin (A2547, Sigma-Aldrich), claudin 1 (51-9000, Thermo Fisher Scientific, MA, USA), cytochrome c oxidase polypeptide IV (COX4) (PM063, Medical & Biological Laboratories, Nagoya, Japan), collagen I (ab34710, Abcam), and calbindin D28k (214004, Synaptic Systems, Goettingen, Germany). For the detection of myosin-11, α-smooth muscle actin, claudin 1, COX4, collagen I, and calbindin D28k staining, paraffin-embedded embryonic mice kidney sections were immunologically stained as described previously [46][47][48][49][50][51] . The images shown in Figs.…”

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confidence: 99%

Single cell RNA sequencing uncovers cellular developmental sequences and novel potential intercellular communications in embryonic kidney

Matsui

Matsumoto

Inoue

et al. 2021

Sci Rep

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Kidney development requires the coordinated growth and differentiation of multiple cells. Despite recent single cell profiles in nephrogenesis research, tools for data analysis are rapidly developing, and offer an opportunity to gain additional insight into kidney development. In this study, single-cell RNA sequencing data obtained from embryonic mouse kidney were re-analyzed. Manifold learning based on partition-based graph-abstraction coordinated cells, reflecting their expected lineage relationships. Consequently, the coordination in combination with ForceAtlas2 enabled the inference of parietal epithelial cells of Bowman’s capsule and the inference of cells involved in the developmental process from the S-shaped body to each nephron segment. RNA velocity suggested developmental sequences of proximal tubules and podocytes. In combination with a Markov chain algorithm, RNA velocity suggested the self-renewal processes of nephron progenitors. NicheNet analyses suggested that not only cells belonging to ureteric bud and stroma, but also endothelial cells, macrophages, and pericytes may contribute to the differentiation of cells from nephron progenitors. Organ culture of embryonic mouse kidney demonstrated that nerve growth factor, one of the nephrogenesis-related factors inferred by NicheNet, contributed to mitochondrial biogenesis in developing distal tubules. These approaches suggested previously unrecognized aspects of the underlying mechanisms for kidney development.

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“…Six-week-old male Sprague-Dawley rats and eight-week-old male C57BL/6 mice were purchased from Japan SLC Inc. (Shizuoka, Japan) and maintained at the animal facility of Osaka University School of Medicine. 26,27 Puromycin aminonucleoside (PAN) nephrosis was induced in the rats with a single intravenous injection of PAN (Sigma-Aldrich, MO, USA) dissolved in saline at a dose of 10 mg/100 g body weight.…”

Section: Animalsmentioning

confidence: 99%

Quantitative Analyses of Foot Processes, Mitochondria, and Basement Membranes by Structured Illumination

Matsumoto

Matsui

Katsuma

et al. 2021

Kidney International Reports

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Lithocholic acid increases intestinal phosphate and calcium absorption in a vitamin D receptor dependent but transcellular pathway independent manner

Cited by 38 publications

References 49 publications

1,25(OH)₂ vitamin D₃ stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

1,25(OH)₂ vitamin D₃ stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

Single cell RNA sequencing uncovers cellular developmental sequences and novel potential intercellular communications in embryonic kidney

Quantitative Analyses of Foot Processes, Mitochondria, and Basement Membranes by Structured Illumination

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Lithocholic acid increases intestinal phosphate and calcium absorption in a vitamin D receptor dependent but transcellular pathway independent manner

Cited by 38 publications

References 49 publications

1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

Single cell RNA sequencing uncovers cellular developmental sequences and novel potential intercellular communications in embryonic kidney

Quantitative Analyses of Foot Processes, Mitochondria, and Basement Membranes by Structured Illumination

Contact Info

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1,25(OH)₂ vitamin D₃ stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

1,25(OH)₂ vitamin D₃ stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine