Transcription factor MafB may play an important role in secondary hyperparathyroidism.

Abstract

The transcription factor MafB is essential for development of the parathyroid glands, the expression of which persists after morphogenesis and in adult parathyroid glands. However, the function of MafB in adult parathyroid tissue is unclear. To investigate this, we induced chronic kidney disease (CKD) in wild-type and MafB heterozygote (MafB+/-) mice by feeding them an adenine-supplemented diet, leading to secondary hyperparathyroidism. The elevated serum creatinine and blood urea nitrogen levels in heterozygous and wild-type mice fed the adenine-supplemented diet were similar. Interestingly, secondary hyperparathyroidism, characterized by serum parathyroid hormone elevation and enlargement of parathyroid glands, was suppressed in MafB+/- mice fed the adenine-supplemented diet compared to similarly fed wild-type littermates. Quantitative RT-PCR and immunohistochemical analyses showed that the increased expression of parathyroid hormone and cyclin D2 in mice with CKD was suppressed in the parathyroid glands of heterozygous CKD mice. A reporter assay indicated that MafB directly regulated parathyroid hormone and cyclin D2 expression. To exclude an effect of a developmental anomaly in MafB+/- mice, we analyzed MafB tamoxifen-induced global knockout mice. Hypocalcemia-stimulated parathyroid hormone secretion was significantly impaired in MafB knockout mice. RNA-sequencing analysis indicated PTH, Gata3 and Gcm2 depletion in the parathyroid glands of MafB knockout mice. Thus, MafB appears to play an important role in secondary hyperparathyroidism by regulation of parathyroid hormone and cyclin D2 expression. Hence, MafB may represent a new therapeutic target in secondary hyperparathyroidism.

• Authors: Naoki Morito, Keigyou Yoh, Toshiaki Usui, Hisashi Oishi, Masami Ojima, Akiko Fujita, Ryusuke Koshida, Hossam H Shawki, Michito Hamada, Masafumi Muratani, Kunihiro Yamagata, Satoru Takahashi
• Journal: Kidney international (Kidney Int) Vol. 93 Issue 1 Pg. 54-68 (01 2018) ISSN: 1523-1755 [Electronic] United States
• PMID: 28964572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Ccnd2 protein, mouse
• Cyclin D2
• MafB Transcription Factor
• Mafb protein, mouse
• Parathyroid Hormone
• Creatinine
• Calcium

Topics

• Animals
• Blood Urea Nitrogen
• Calcium (blood)
• Creatinine (blood)
• Cyclin D2 (genetics, metabolism)
• Disease Models, Animal
• Gene Expression Regulation
• Hyperparathyroidism, Secondary (blood, genetics, metabolism, pathology)
• Hypocalcemia (genetics, metabolism)
• MafB Transcription Factor (deficiency, genetics, metabolism)
• Mice, 129 Strain
• Mice, Inbred C57BL
• Mice, Knockout
• Parathyroid Glands (metabolism, pathology)
• Parathyroid Hormone (blood, genetics)