Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes

被引:377
作者
Fujita, Hiroki [1 ,2 ]
Sugimoto, Kotaro [1 ]
Inatomi, Shuichiro [1 ]
Maeda, Toshihiro [1 ]
Osanai, Makoto [1 ]
Uchiyama, Yasushi [3 ]
Yamamoto, Yoko [4 ]
Wada, Takuro [2 ]
Kojima, Takashi [1 ]
Yokozaki, Hiroshi [5 ]
Yamashita, Toshihiko [2 ]
Kato, Shigeaki [4 ]
Sawada, Norimasa [1 ]
Chiba, Hideki [1 ]
机构
[1] Sapporo Med Univ, Sch Med, Dept Pathol, Sapporo, Hokkaido 0608556, Japan
[2] Sapporo Med Univ, Sch Med, Dept Orthoped Surg, Sapporo, Hokkaido 0608556, Japan
[3] Chugai Pharmaceut Co Ltd, Tokyo 1048301, Japan
[4] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan
[5] Kobe Univ, Grad Sch Med, Div Surg Pathol, Dept Biomed Informat, Kobe, Hyogo 6500017, Japan
关键词
D O I
10.1091/mbc.E07-09-0973
中图分类号
Q2 [细胞生物学];
学科分类号
071009 [细胞生物学]; 090102 [作物遗传育种];
摘要
Ca(2+) is absorbed across intestinal epithelial monolayers via transcellular and paracellular pathways, and an active form of vitamin D(3), 1 alpha,25-dihydroxyvitamin D(3) [1 alpha,25(OH)(2)D(3)], is known to promote intestinal Ca(2+) absorption. However, the molecules driving the paracellular Ca(2+) absorption and its vitamin D dependency remain obscure. Because the tight junction proteins claudins are suggested to form paracellular channels for selective ions between neighboring cells, we hypothesized that specific intestinal claudins might facilitate paracellular Ca(2+) transport and that expression of these claudins could be induced by 1 alpha, 25(OH)(2)D(3). Herein, we show, by using RNA interference and overexpression strategies, that claudin-2 and claudin-12 contribute to Ca(2+) absorption in intestinal epithelial cells. We also provide evidence showing that expression of claudins-2 and -12 is up-regulated in enterocytes in vitro and in vivo by 1 alpha,25(OH)(2)D(3) through the vitamin D receptor. These findings strongly suggest that claudin-2- and/or claudin-12-based tight junctions form paracellular Ca(2+) channels in intestinal epithelia, and they highlight a novel mechanism behind vitamin D-dependent calcium homeostasis.
引用
收藏
页码:1912 / 1921
页数:10
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