Duodenal calcium absorption in vitamin D receptor–knockout mice: Functional and molecular aspects

DOI HANDLE HANDLE Web Site PubMed 被引用文献30件 オープンアクセス
  • Sophie J. Van Cromphaut
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
  • Mieke Dewerchin
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
  • Joost G. J. Hoenderop
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
  • Ingrid Stockmans
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
  • Erik Van Herck
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
  • Shigeaki Kato
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
  • René J. M. Bindels
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
  • Désiré Collen
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
  • Peter Carmeliet
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
  • Roger Bouillon
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan
  • Geert Carmeliet
    Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, B-3000 Belgium; Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven, B-3000 Belgium; Department of Cell Physiology, Institute of Cellular Signaling, University Medical Centre Nijmegen, NL-6500-HB The Netherlands; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan

説明

<jats:p> Rickets and hyperparathyroidism caused by a defective vitamin D receptor (VDR) can be prevented in humans and animals by high calcium intake, suggesting that intestinal calcium absorption is critical for 1,25(OH) <jats:sub>2</jats:sub> vitamin D [1,25(OH) <jats:sub>2</jats:sub> D <jats:sub>3</jats:sub> ] action on calcium homeostasis. We assessed the rate of serum <jats:sup>45</jats:sup> Ca accumulation within 10 min of oral gavage in two strains of VDR-knockout (KO) mice (Leuven and Tokyo KO) and observed a 3-fold lower area under the curve in both KO strains. Moreover, we evaluated the expression of intestinal candidate genes involved in transcellular calcium transport. The calcium transport protein1 (CaT1) was more abundantly expressed at mRNA level than the epithelial calcium channel (ECaC) in duodenum, but both were considerably reduced (CaT1>90%, ECaC>60%) in the two VDR-KO strains on a normal calcium diet. Calbindin-D <jats:sub>9K</jats:sub> expression was decreased only in the Tokyo KO, whereas plasma membrane calcium ATPase (PMCA <jats:sub>1b</jats:sub> ) expression was normal in both VDR-KOs. In Leuven wild-type mice, a high calcium diet inhibited (>90%) and 1,25(OH) <jats:sub>2</jats:sub> D <jats:sub>3</jats:sub> injection or low calcium diet induced (6-fold) duodenal CaT1 expression and, to a lesser degree, ECaC and calbindin-D <jats:sub>9K</jats:sub> expression. In Leuven KO mice, however, high or low calcium intake decreased calbindin-D <jats:sub>9K</jats:sub> and PMCA <jats:sub>1b</jats:sub> expression, whereas CaT1 and ECaC expression remained consistently low on any diet. These results suggest that the expression of the novel duodenal epithelial calcium channels (in particular CaT1) is strongly vitamin D-dependent, and that calcium influx, probably interacting with calbindin-D <jats:sub>9K</jats:sub> , should be considered as a rate-limiting step in the process of vitamin D-dependent active calcium absorption. </jats:p>

収録刊行物

被引用文献 (30)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ