Effects of 1, 25-dihydroxyvitamin D3 on the synthesis of DNA and glycosaminoglycans by rat aortic smooth muscle cells in vitro

Koh, Eio; Morimoto, Shigeto; Nabata, T; Takamoto, Shoshi; Kitano, Shiro; Ogihara, Toshio

doi:10.1016/0024-3205(90)90428-t

Cited by 14 publications

(4 citation statements)

References 15 publications

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“…VDR s which are DNA-linked proteins (Mitsuhashi et al 1991) were identified in SMCs in vitro (Kawashima 1987, Merke et al1987, Koh et al 1988. Stimulation of these receptors induce cell proliferation and differentiation in several tissues (Pike 1985, Pols et al 1990, Walters 1992, and there is an increase in DNA synthesis and a decrease in heparan sulfate, a glycosaminoglycan responsible for the inhibition of the proliferation of these cells, allowing multiplication of the SMCs (Koh et al 1990). …”

Section: Discussionmentioning

confidence: 99%

Arterial diffuse intimal thickening associated with enzootic calcinosis of sheep

et al. 1998

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Pesq. Vet. Bras. 18(1):9-15, jan./mar. 1998 9 RESUMO.-[Espessamento intimal difuso das artérias na calcinose enzoótica dos ovinos.] Foram feitos estudos morfométrico, imunoistoquímico e ultra-estrutural do espessamento intimal difuso (DIT) das artérias de 7 ovinos com sinais clínicos de calcinose enzoótica espontânea causada pela ingestão da planta Nierembergia veitchii. As lesões caracterizavam-se por deposição de sais de cálcio na média como placas e estrias que, com frequência faziam saliência para a luz, criando rugosidades e irregularidades da íntima. Não foram observadas calcificações na artéria pulmonar e no sistema venoso. Microscopicamente, as calcificações das artéri-as restringiam-se quase que exclusivamente à média. Na imunoistoquimica, foi verificada α-actina nas células da mé-dia e nas do espessamento intimal. Receptores para 1,25(OH) 2 D 3 foram evidenciados nos núcleos das células musculares da média, da íntima e das células endoteliais. As aná-lises morfométricas em microscopia ótica revelaram, nas artérias, DIT irregularmente distribuido sem relação com a intensidade dos processos de calcificação subjacente nem com a espessura da média remanescente. A morfometria das alterações ultra-estruturais das células musculares lisas da mé-dia e da íntima espessada, mostrou que nessas últimas foi verificado aumento de até 318% na fração volumétrica das organelas de síntese em detrimento dos elementos contráteis, Morphometric, immunohistochemical and ultrastructural studies were carried out on the diffuse intimal thickening (DIT) in arteries of 7 sheep with clinical signs of naturally occurring enzootic calcinosis due to ingestion of the plant Nierembergia veitchii. Arterial lesions consisted of medial deposition of calcium salts and DIT. Calcification of the intima was rare, mild and located near the elastic lamina. By immunohistochemistry α-actin was detected in cells of the media and in cells forming the intimal thickening. Receptors for 1,25(OH) 2 vitamin D 3 were detected in nuclei of intimal, medial and endothelial cells. DIT was irregularly distributed and was neither proportionally related to the intensity of the underlying mineralization area nor to the thickening of the remaining media. Ultrastructural morphometry in smooth muscle cells (SMCs) of the media and thickened intima revealed, in the latter, an increase of 318% in the volumetric fraction of those organelles involved in synthesis and a proportional decrease in contractile elements when compared to normal values of media cells. There were histological and ultrastructural evidences of modification of SMCs and their migration to the intima, where they proliferated causing DIT. It was concluded that DIT is a consistent component of arteriosclerotic lesions in N. veitchii induced calcinosis of sheep and that the predominant cell in this process is the SMCs originated from its predecessors of the media. It is suggested that the inducing factor for the arterial changes is 1,25(OH) 2 D 3 present in N. veitchii.

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Section: Discussionmentioning

confidence: 99%

Arterial diffuse intimal thickening associated with enzootic calcinosis of sheep

et al. 1998

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“…This active metabolite of vitamin D appears to cause cell cycle arrest and inhibit proliferation of most cell types [3,4]. The mitogenic role of calcitriol in aortal SMCs culture has been previously reported although obtained results are limited and controversial [5][6][7]. The aim of this study was to determine * Corresponding author.…”

Section: Introductionmentioning

confidence: 95%

Quantifying division of aortal smooth muscle cells in culture stimulated by 1,25(OH)2D3

Tukaj

Trzonkowski

Kubasik-Juraniec

et al. 2007

The Journal of Steroid Biochemistry and Molecular Biology

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“…15,16 In particular, 1␣,25-(OH) 2 D 3 has been shown to regulate calcium homeostasis, modulate growth, and increase calcification in smooth muscle cells. [17][18][19] Indeed, the mitogenic role of 1␣,25-(OH) 2 D 3 in VSMCs has been previously reported, 18,20,21 although its effect on the migration has not been investigated. Therefore, the purpose of this study was to determine whether 1␣,25-(OH) 2 D 3 can promote SMC migration, and if so, to determine whether the mechanism is mediated by the genomic or nongenomic effects of VDR.…”

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confidence: 99%

1α,25-Dihydroxyvitamin D ₃ Induces Vascular Smooth Muscle Cell Migration via Activation of Phosphatidylinositol 3-Kinase

Rebsamen

Sun

Norman

et al. 2002

Circulation Research

150

102

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(VDRE). 2 VDR belongs to the nuclear receptor superfamily for steroid hormones, retinoic acid, and thyroid hormone (T 4 ). 3 These receptors bind to their responsive elements and alter downstream gene transcription. In addition, 1␣,25-(OH) 2 D 3 has also been shown to produce rapid, nongenomic (ie, VDRE-independent) responses. 4 Indeed, 1␣,25-(OH) 2 D 3 stimulates a wide array of rapid responses including rapid intestinal absorption of calcium (transcaltachia), 5 store-operated calcium influx, 6 activation of protein kinase C, 7 and opening of voltage-gated calcium and chloride channels. 8 Although the precise molecular mechanisms by which these rapid nongenomic responses are regulated remain unclear, a putative membrane receptor for 1␣,25-(OH) 2 D 3 or alternative pathways of the nuclear VDR have been proposed. 9 Analogs of 1␣,25-(OH) 2 D 3 have been used to differentiate the genomic (ie, VDRE-dependent) versus nongenomic responses. These analogs take advantage of the flexible conformation of 1␣,25-(OH) 2 D 3 at the 6,7 carboncarbon single bond (Figure 1). Rapid rotation about this bond allows generation of a continuum of various shapes of 1␣,25-(OH) 2 D 3 ranging from the planar extended 6-s-trans conformation to the steroid-like 6-s-cis conformation 10,11 ; these various shapes are then available to serve as ligands for appropriate receptors. Indeed, the 6-s-cis-locked analog 1␣,25-dihydroxylumisterol is a fully potent agonist of rapid, nongenomic responses of 1␣,25-(OH) 2 D 3 . 5 Thus, it has been proposed that different shapes of the conformationally flexible 1␣,25-(OH) 2 D 3 are agonists for the rapid, nongenomic (6-s-cis) and genomic (twisted 6-s-trans) responses. 12 In addition, analogs that antagonize 1␣,25-(OH) 2 D 3 responses have also been characterized. Indeed, 1␤,25-(OH) 2 D 3 (HL) is a specific antagonist of nongenomic action of 1␣,25-(OH) 2 D 3 , 8,13 whereas (23S)-25-dehydro-1␣-OH-D 3 -26,23-lactone (MK) preferentially inhibits genomic responses. 14 Original

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Effects of 1, 25-dihydroxyvitamin D3 on the synthesis of DNA and glycosaminoglycans by rat aortic smooth muscle cells in vitro

Cited by 14 publications

References 15 publications

Arterial diffuse intimal thickening associated with enzootic calcinosis of sheep

Arterial diffuse intimal thickening associated with enzootic calcinosis of sheep

Quantifying division of aortal smooth muscle cells in culture stimulated by 1,25(OH)2D3

1α,25-Dihydroxyvitamin D ₃ Induces Vascular Smooth Muscle Cell Migration via Activation of Phosphatidylinositol 3-Kinase

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Effects of 1, 25-dihydroxyvitamin D3 on the synthesis of DNA and glycosaminoglycans by rat aortic smooth muscle cells in vitro

Cited by 14 publications

References 15 publications

Arterial diffuse intimal thickening associated with enzootic calcinosis of sheep

Arterial diffuse intimal thickening associated with enzootic calcinosis of sheep

Quantifying division of aortal smooth muscle cells in culture stimulated by 1,25(OH)2D3

1α,25-Dihydroxyvitamin D 3 Induces Vascular Smooth Muscle Cell Migration via Activation of Phosphatidylinositol 3-Kinase

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1α,25-Dihydroxyvitamin D ₃ Induces Vascular Smooth Muscle Cell Migration via Activation of Phosphatidylinositol 3-Kinase