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Interrelated role of Klotho and calcium-sensing receptor in parathyroid hormone synthesis and parathyroid hyperplasia.
Fan, Yi; Liu, Weiqing; Bi, Ruiye; Densmore, Michael J; Sato, Tadatoshi; Mannstadt, Michael; Yuan, Quan; Zhou, Xuedong; Olauson, Hannes; Larsson, Tobias E; Toka, Hakan R; Pollak, Martin R; Brown, Edward M; Lanske, Beate.
Afiliación
  • Fan Y; Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA 02115.
  • Liu W; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 Sichuan, China.
  • Bi R; Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA 02115.
  • Densmore MJ; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 Sichuan, China.
  • Sato T; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 Sichuan, China.
  • Mannstadt M; Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
  • Yuan Q; Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA 02115.
  • Zhou X; Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA 02115.
  • Olauson H; Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
  • Larsson TE; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 Sichuan, China.
  • Toka HR; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 Sichuan, China.
  • Pollak MR; Division of Renal Medicine, Clinical Sciences, Intervention and Technology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Brown EM; Division of Renal Medicine, Clinical Sciences, Intervention and Technology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Lanske B; Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A ; 115(16): E3749-E3758, 2018 04 17.
Article en En | MEDLINE | ID: mdl-29618612
The pathogenesis of parathyroid gland hyperplasia is poorly understood, and a better understanding is essential if there is to be improvement over the current strategies for prevention and treatment of secondary hyperparathyroidism. Here we investigate the specific role of Klotho expressed in the parathyroid glands (PTGs) in mediating parathyroid hormone (PTH) and serum calcium homeostasis, as well as the potential interaction between calcium-sensing receptor (CaSR) and Klotho. We generated mouse strains with PTG-specific deletion of Klotho and CaSR and dual deletion of both genes. We show that ablating CaSR in the PTGs increases PTH synthesis, that Klotho has a pivotal role in suppressing PTH in the absence of CaSR, and that CaSR together with Klotho regulates PTH biosynthesis and PTG growth. We utilized the tdTomato gene in our mice to visualize and collect PTGs to reveal an inhibitory function of Klotho on PTG cell proliferation. Chronic hypocalcemia and ex vivo PTG culture demonstrated an independent role for Klotho in mediating PTH secretion. Moreover, we identify an interaction between PTG-expressed CaSR and Klotho. These findings reveal essential and interrelated functions for CaSR and Klotho during parathyroid hyperplasia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hormona Paratiroidea / Glándulas Paratiroides / Receptores Acoplados a Proteínas G / Glucuronidasa Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hormona Paratiroidea / Glándulas Paratiroides / Receptores Acoplados a Proteínas G / Glucuronidasa Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos