دورية أكاديمية
Zona Glomerulosa-Derived Klotho Modulates Aldosterone Synthase Expression in Young Female Mice.
| العنوان: | Zona Glomerulosa-Derived Klotho Modulates Aldosterone Synthase Expression in Young Female Mice. |
|---|---|
| المؤلفون: | Daryadel A; Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zürich (USZ) and University of Zürich (UZH), 8091 Zurich, Switzerland., Tang C; Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zürich (USZ) and University of Zürich (UZH), 8091 Zurich, Switzerland., Xie Y; Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zürich (USZ) and University of Zürich (UZH), 8091 Zurich, Switzerland., Peitzsch M; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany., Fisi V; Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zürich (USZ) and University of Zürich (UZH), 8091 Zurich, Switzerland., Hantel C; Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zürich (USZ) and University of Zürich (UZH), 8091 Zurich, Switzerland., Loffing-Cueni D; Institute of Anatomy, University of Zürich, 8057 Zurich, Switzerland., Breault DT; Division of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Penton D; Electrophysiology Facility, University of Zurich, 8057 Zürich, Switzerland., Loffing J; Institute of Anatomy, University of Zürich, 8057 Zurich, Switzerland., Beuschlein F; Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zürich (USZ) and University of Zürich (UZH), 8091 Zurich, Switzerland.; Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität, 81377 Munich, Germany.; The LOOP Zurich Medical Research Center, 8044 Zurich, Switzerland. |
| المصدر: | Endocrinology [Endocrinology] 2024 Mar 29; Vol. 165 (5). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375040 Publication Model: Print Cited Medium: Internet ISSN: 1945-7170 (Electronic) Linking ISSN: 00137227 NLM ISO Abbreviation: Endocrinology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Los Angeles, Calif. : Association for the Study of Internal Secretions, |
| مواضيع طبية MeSH: | Adrenal Cortex*/metabolism , Hyperaldosteronism*/genetics, Female ; Mice ; Animals ; Zona Glomerulosa/metabolism ; Cytochrome P-450 CYP11B2/genetics ; Cytochrome P-450 CYP11B2/metabolism ; Aldosterone/metabolism ; Tamoxifen/pharmacology |
| مستخلص: | Klotho plays a critical role in the regulation of ion and fluid homeostasis. A previous study reported that haplo-insufficiency of Klotho in mice results in increased aldosterone synthase (CYP11B2) expression, elevated plasma aldosterone, and high blood pressure. This phenotype was presumed to be the result of diminished Klotho expression in zona glomerulosa (zG) cells of the adrenal cortex; however, systemic effects on adrenal aldosterone production could not be ruled out. To examine whether Klotho expressed in the zG is indeed a critical regulator of aldosterone synthesis, we generated a tamoxifen-inducible, zG-specific mouse model of Klotho deficiency by crossing Klotho-flox mice with Cyp11b2-CreERT mice (zG-Kl-KO). Tamoxifen-treated Cyp11b2-CreERT animals (zG-Cre) served as controls. Rosa26-mTmG reporter mice were used for Cre-dependent lineage-marking. Two weeks after tamoxifen induction, the specificity of the zG-Cre line was verified using immunofluorescence analysis to show that GFP expression was restricted to the zG. RNA in situ hybridization revealed a 65% downregulation of Klotho messenger RNA expression in the zG of zG-Kl-KO female mice at age 12 weeks compared to control mice. Despite this significant decrease, zG-Kl-KO mice exhibited no difference in plasma aldosterone levels. However, adrenal CYP11B2 expression and the CYP11B2 promotor regulatory transcription factors, NGFIB and Nurr1, were enhanced. Together with in vitro experiments, these results suggest that zG-derived Klotho modulates Cyp11b2 but does not evoke a systemic phenotype in young adult mice on a normal diet. Further studies are required to investigate the role of adrenal Klotho on aldosterone synthesis in aged animals. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.) |
| References: | J Clin Endocrinol Metab. 2004 Aug;89(8):4113-8. (PMID: 15292355) Horm Metab Res. 2013 Feb;45(2):124-9. (PMID: 23111829) PLoS One. 2013 Aug 14;8(8):e70775. (PMID: 23967103) Endocrinology. 2024 Mar 29;165(5):. (PMID: 38573585) Nephrol Dial Transplant. 2018 Oct 1;33(10):1722-1734. (PMID: 29425341) Pediatr Nephrol. 2021 Oct;36(10):3007-3022. (PMID: 33230698) Am J Physiol Renal Physiol. 2010 Nov;299(5):F1171-7. (PMID: 20719979) Genesis. 2007 Sep;45(9):593-605. (PMID: 17868096) J Clin Invest. 2013 Feb;123(2):812-22. (PMID: 23298834) Cells. 2022 Apr 24;11(9):. (PMID: 35563746) J Am Soc Nephrol. 2016 Jun;27(6):1765-76. (PMID: 26471128) J Clin Invest. 2011 Nov;121(11):4393-408. (PMID: 21985788) Heliyon. 2020 Mar 10;6(3):e03519. (PMID: 32181392) Science. 2005 Sep 16;309(5742):1829-33. (PMID: 16123266) Alcohol Res. 2012;34(4):468-83. (PMID: 23584113) JCI Insight. 2023 Jul 24;8(14):. (PMID: 37310791) Endocrinology. 2005 Feb;146(2):633-42. (PMID: 15539557) Pflugers Arch. 2010 Jan;459(2):333-43. (PMID: 19730882) Nat Rev Nephrol. 2019 Jan;15(1):27-44. (PMID: 30455427) Physiol Genomics. 2004 Sep 16;19(1):106-16. (PMID: 15375197) Am J Physiol Heart Circ Physiol. 2014 Nov 15;307(10):H1504-11. (PMID: 25217649) Biochem Biophys Res Commun. 2016 Feb 5;470(2):384-390. (PMID: 26773502) Dialogues Clin Neurosci. 2006;8(4):383-95. (PMID: 17290797) Annu Rev Physiol. 2013;75:503-33. (PMID: 23398153) Nephrol Dial Transplant. 2022 Jan 25;37(2):211-221. (PMID: 34459924) Nat Commun. 2020 Apr 3;11(1):1680. (PMID: 32245949) Mol Cell Endocrinol. 2007 Feb;265-266:126-30. (PMID: 17215073) Mol Endocrinol. 2004 Feb;18(2):279-90. (PMID: 14645496) J Mol Endocrinol. 2017 Feb;58(2):67-78. (PMID: 27965370) J Steroid Biochem Mol Biol. 2015 Jan;145:75-84. (PMID: 25312486) Nature. 1997 Nov 6;390(6655):45-51. (PMID: 9363890) PLoS One. 2013 Jun 25;8(6):e66182. (PMID: 23825530) |
| معلومات مُعتمدة: | Switzerland SNSF_ Swiss National Science Foundation |
| فهرسة مساهمة: | Keywords: CYP11B2; Cre-lox system; Klotho; aldosterone; zona glomerulosa |
| المشرفين على المادة: | EC 1.14.15.4 (Cytochrome P-450 CYP11B2) 4964P6T9RB (Aldosterone) 094ZI81Y45 (Tamoxifen) |
| تواريخ الأحداث: | Date Created: 20240404 Date Completed: 20240410 Latest Revision: 20240430 |
| رمز التحديث: | 20240430 |
| مُعرف محوري في PubMed: | PMC11002783 |
| DOI: | 10.1210/endocr/bqae040 |
| PMID: | 38573585 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-7170 |
|---|---|
| DOI: | 10.1210/endocr/bqae040 |