Metabolism and sites of action of vitamin D in the kidney

Kawashima, Hiroyuki; Kurokawa, Kiyoshi

doi:10.1038/ki.1986.12

Cited by 46 publications

(17 citation statements)

References 82 publications

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“…(c) IGF 1 (25 ng/ml) increased 1,25(OH)2D3 production in rabbit's cells, particularly in phosphate-free medium (1.6-fold), and in LLC-PK 1 cells, in partial phosphate depletion (2.75-fold in 1 mM phosphate, P = 0.015, n = 5, and 3.2-fold in 0.5 mM phosphate, P = 0.043, n = 4). Our findings demonstrate a local action of phosphate depletion and of IGF 1 (6)(7)(8)(9)(10)(11). Phosphate is a particularly interesting regulator of laOHase: in animals and in humans (6,7,9,10,12,13), dietary phosphate restriction or low phosphate serum concentrations lead to an increase of plasma 1,25-(OH)2D concentration, but in vitro no direct effect of phosphate depletion on 1,25-(OH)2D3 production has so far been evidenced (14,15).…”

Section: Nm Of [3h]25(oh)d3 or 2 Um Of 25(0oh))d3mentioning

confidence: 85%

“…This lack of expression may result from the conditions used in this study, or may be an argument in favor of the pars recta origin of the OK cells, as the 25-(OH)D3-laOHase has been mainly localized in the proximal convoluted tubules in chick and rat kidneys (8). In contrast, LLC-PK 1 cells and rabbit's cells in primary culture expressed a clear 25-(OH)D3-laOHase activity, and thus proved to be new useful models for studying the laOHase enzymatic system.…”

Section: Discussionmentioning

confidence: 97%

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Local action of phosphate depletion and insulin-like growth factor 1 on in vitro production of 1,25-dihydroxyvitamin D by cultured mammalian kidney cells.

Condamine¹,

Menaa²,

Vrtovsnik³

et al. 1994

J. Clin. Invest.

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Section: Nm Of [3h]25(oh)d3 or 2 Um Of 25(0oh))d3mentioning

confidence: 85%

Section: Discussionmentioning

confidence: 97%

Local action of phosphate depletion and insulin-like growth factor 1 on in vitro production of 1,25-dihydroxyvitamin D by cultured mammalian kidney cells.

Condamine¹,

Menaa²,

Vrtovsnik³

et al. 1994

J. Clin. Invest.

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“…CT maintained plasma calcium homeostasis as follows: CT acted on CTR, and raised the calcium level by generated 1a,25(OH) 2 D 3 in the proximal straight tubule [23]. As there is no adenylate cyclase activity in the proximal tubule, it is conjectured that the signal transduction is not likely to be mediated by cAMP [12,30]. In the proximal tubule, the presence of parathyroid hormone (PTH) receptor mRNA has been demonstrated [19,29], suggesting that the expression of both CTR and PTH receptor in the proximal tubule might play an important role in calcium homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Localization of Calcitonin Receptor mRNA in Rat Kidney: an In Situ Hybridization Study

Ishii

Nakamura

et al. 2004

Acta Histochem. Cytochem

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Calcitonin (CT) enhances calcium excretion by inhibition of renal tubular calcium resorption, but the precise functions of CT remain poorly understood. We carried out in situ hybridization (ISH) for the calcitonin receptor (CTR) to evaluate the site that expresses CTR mRNA in the rat kidney. The intense signal was observed in the straight tubule of the cortex and the outer stripe of the outer medulla, but not in the inner medulla. A less intense signal was observed in the convoluted and collecting tubules, glomeruli, and renal tubule of the inner stripe of the outer medulla. Although CTR expression in the proximal straight tubule was suggested based on the physiological evidence, CTR localization was not proven. We demonstrated CTR expression in the proximal straight tubule, in addition to the distal straight tubule reported in previous studies using autoradiography. It was not possible to distinguish two CTR isoforms (C1a and C1b) by ISH, because a new probe recognized the common sequence of these isoforms. As only C1a was confirmed in kidney by RT-PCR, it seems reasonably certain that the ISH signal is of the C1a type. This new CTR probe can be an important tool for analyzing CTR expression in various tissues.

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“…The activity of 1␣-hydroxylase is most abundant in the renal proximal tubular cells (1,(3)(4)(5), and our previous studies showed gene expression of 1␣-hydroxylase to be restricted to the kidney (9,15). To investigate the mechanism responsible for this cell-specific expression, we first examined the expression of 1␣-hydroxylase gene in cultured cell lines by Northern blot analyses.…”

Section: Only Llc-pk1 Cells Express the 1␣-hydroxylase Genementioning

confidence: 99%

“…Its enzyme activity is tightly regulated by several factors including parathyroid hormone, 1␣,25-(OH) 2 D itself, calcitonin, and serum concentrations of calcium and phosphate (2). Most of the studies to date have demonstrated that renal 1␣-hydroxylase activity is localized exclusively in the proximal tubules (3)(4)(5).…”

mentioning

confidence: 99%

Identification of a Renal Proximal Tubular Cell-Specific Enhancer in the Mouse 25-Hydroxyvitamin D 1α-Hydroxylase Gene

Yoshida

Yoshino

Hayashi

et al. 2002

Journal of the American Society of Nephrology

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Abstract. The active form of vitamin D is synthesized by 25-hydroxyvitamin D 1␣-hydroxylase (1␣-hydroxylase), which is expressed predominantly in renal proximal tubular cells. To clarify the mechanism of cell-specific gene expression of this enzyme, the 5'-flanking region of the mouse 1␣-hydroxylase gene was investigated. Investigation began with mRNA expression of 1␣-hydroxylase in cultured cells, including LLC-PK1, NIH/3T3, HepG2, MDCK, and OK cells. Expression of 1␣-hydroxylase mRNA was restricted in LLC-PK1 cells. Several lengths of the 5'-flanking region of 1␣-hydroxylase gene were linked to a pGL3-basic luciferase vector and introduced into these cells. Only LLC-PK1 cells had a substantial luciferase activity. Deletion analyses revealed that luciferase activity was detected in constructs extending from the transcription initiation site to Ϫ1652 to Ϫ105 bp, whereas further deletion to Ϫ80 bp resulted in a marked decrease in activity. The region from Ϫ105 to Ϫ80 bp contained two ternary complex factor-1 (TCF-1) sites, and mutations in the proximal TCF-1 site decreased the activity. Electrophoretic mobility shift assay demonstrated binding of LLC-PK1 nuclear proteins to this region. Tests of enhancer function in LLC-PK1 cells indicated that the 26-bp fragment behaved as a classical enhancer, i.e., independently of position and orientation. Moreover, a decoy oligonucleotide corresponding to this region substantially inhibited the promoter activity of 1␣-hydroxylase gene. This study suggests that the Ϫ105 to Ϫ80 bp element of mouse 1␣-hydroxylase gene contains an enhancer to be necessary for renal proximal tubular cell-specific expression. We and other investigators have recently cloned rat (6,7), mouse (8), human (9,10), and porcine (11) cDNAs of 1␣-hydroxylase. The complete sequences of mouse and human 1␣-hydroxylase genes have also been reported (9,(12)(13)(14). It has been demonstrated that mutations in the 1␣-hydroxylase gene cause vitamin D dependency rickets type I, which is characterized by early onset of hypocalcemia, secondary hyperparathyroidism, and severe rachitic lesions (10,15,16). Northern blot analyses have revealed 1␣-hydroxylase mRNA expression to be localized mainly in the kidney (9,15). This result is consistent with the previous studies that the kidney is the principal site of 1␣,25-(OH) 2 D synthesis, although several extrarenal cells, including keratinocytes (17), placental decidual cells (18), and pulmonary macrophages (19) also have 1␣-hydroxylase activity. Extrarenal 1␣-hydroxylase does not contribute to circulating 1␣,25-(OH) 2 D concentrations and acts in an intracrine manner.The mechanism that the 1␣-hydroxylase gene is predominantly expressed in renal proximal tubular cells clearly warrants study. Little is known about proximal tubular cell-specific gene expression, although several investigations have focused on the mechanism responsible for the kidney-specificity or other nephron segments-specificity (20 -24). We hypothesized that some cell-specific transcriptional regulators bo...

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Metabolism and sites of action of vitamin D in the kidney

Cited by 46 publications

References 82 publications

Local action of phosphate depletion and insulin-like growth factor 1 on in vitro production of 1,25-dihydroxyvitamin D by cultured mammalian kidney cells.

Local action of phosphate depletion and insulin-like growth factor 1 on in vitro production of 1,25-dihydroxyvitamin D by cultured mammalian kidney cells.

Localization of Calcitonin Receptor mRNA in Rat Kidney: an In Situ Hybridization Study

Identification of a Renal Proximal Tubular Cell-Specific Enhancer in the Mouse 25-Hydroxyvitamin D 1α-Hydroxylase Gene

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