Please use this identifier to cite or link to this item: https://doi.org/10.1074/jbc.RA118.007063
Title: Deficiency in the Secreted Protein Semaphorin3d Causes Abnormal Parathyroid Development in Mice.
Authors: ANAMIKA SINGH 
MIA MD MASUM 
DASAN MARY CIBI 
Arya AK
Bhadada SK
Singh Manvendra Kumar 
Issue Date: 24-May-2019
Publisher: American Society for Biochemistry and Molecular Biology Inc.
Citation: ANAMIKA SINGH, MIA MD MASUM, DASAN MARY CIBI, Arya AK, Bhadada SK, Singh Manvendra Kumar (2019-05-24). Deficiency in the Secreted Protein Semaphorin3d Causes Abnormal Parathyroid Development in Mice.. Journal of Biological Chemistry 294 (21) : 8336-8347. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.RA118.007063
Abstract: Primary hyperparathyroidism (PHPT) is a common endocrinopathy characterized by hypercalcemia and elevated levels of parathyroid hormone. The primary cause of PHPT is a benign overgrowth of parathyroid tissue causing excessive secretion of parathyroid hormone. However, the molecular etiology of PHPT is incompletely defined. Here, we demonstrate that semaphorin3d (Sema3d), a secreted glycoprotein, is expressed in the developing parathyroid gland in mice. We also observed that genetic deletion of Sema3d leads to parathyroid hyperplasia, causing PHPT. In vivo and in vitro experiments using histology, immunohistochemistry, biochemical, RT-qPCR, and immunoblotting assays revealed that Sema3d inhibits parathyroid cell proliferation by decreasing the epidermal growth factor receptor (EGFR)/Erb-B2 receptor tyrosine kinase (ERBB) signaling pathway. We further demonstrate that EGFR signaling is elevated in Sema3d-/- parathyroid glands and that pharmacological inhibition of EGFR signaling can partially rescue the parathyroid hyperplasia phenotype. We propose that because Sema3d is a secreted protein, it may be possible to use recombinant Sema3d or derived peptides to inhibit parathyroid cell proliferation causing hyperplasia and hyperparathyroidism. Collectively, these findings identify Sema3d as a negative regulator of parathyroid growth.
Source Title: Journal of Biological Chemistry
URI: https://scholarbank.nus.edu.sg/handle/10635/168454
ISSN: 0021-9258
DOI: 10.1074/jbc.RA118.007063
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