| Autor: |
Hashimoto, Nobuhiro, Matsui, Isao, Ishizuka, Satoshi, Inoue, Kazunori, Matsumoto, Ayumi, Shimada, Karin, Hori, Shota, Lee, Dong Geun, Yasuda, Seiichi, Katsuma, Yusuke, Kajimoto, Sachio, Doi, Yohei, Yamaguchi, Satoshi, Kubota, Keiichi, Oka, Tatsufumi, Sakaguchi, Yusuke, Takabatake, Yoshitsugu, Hamano, Takayuki, Isaka, Yoshitaka |
| Zdroj: |
Kidney International; June 2020, Vol. 97 Issue: 6 p1164-1180, 17p |
| Abstrakt: |
Phosphate/calcium homeostasis is crucial for health maintenance. Lithocholic acid, a bile acid produced by intestinal bacteria, is an agonist of vitamin D receptor. However, its effects on phosphate/calcium homeostasis remain unclear. Here, we demonstrated that lithocholic acid increases intestinal phosphate/calcium absorption in an enterocyte vitamin D receptor-dependent manner. Lithocholic acid was found to increase serum phosphate/calcium levels and thus to exacerbate vascular calcification in animals with chronic kidney disease. Lithocholic acid did not affect levels of intestinal sodium-dependent phosphate transport protein 2b, Pi transporter-1, -2, or transient receptor potential vanilloid subfamily member 6. Everted gut sac analyses demonstrated that lithocholic acid increased phosphate/calcium absorption in a transcellular pathway-independent manner. Lithocholic acid suppressed intestinal mucosal claudin 3 and occludin in wild-type mice, but not in vitamin D receptor knockout mice. Everted gut sacs of claudin 3 knockout mice showed an increased permeability for phosphate, but not calcium. In patients with chronic kidney disease, serum 1,25(OH)2vitamin D levels are decreased, probably as an intrinsic adjustment to reduce phosphate/calcium burden. In contrast, serum and fecal lithocholic acid levels and fecal levels of bile acid 7α-dehydratase, a rate-limiting enzyme involved in lithocholic acid production, were not downregulated. The effects of lithocholic acid were eliminated by bile acid adsorptive resin in mice. Thus, lithocholic acid and claudin 3 may represent novel therapeutic targets for reducing phosphate burden. |
| Databáze: |
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