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Effects of FGF‐23‐mediated ERK/MAPK signaling pathway on parathyroid hormone secretion of parathyroid cells in rats with secondary hyperparathyroidism
Author(s) -
Chen XiaoJun,
Chen Xiong,
Wu WenJun,
Zhou Qi,
Gong XiaoHua,
Shi BiMin
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26525
Subject(s) - parathyroid hormone , medicine , endocrinology , secondary hyperparathyroidism , mapk/erk pathway , apoptosis , chemistry , fibroblast growth factor , hyperparathyroidism , klotho , biology , signal transduction , calcium , receptor , kidney , biochemistry
This study is supposed to investigate the effect of FGF‐23 on parathyroid hormone (PTH) secretion through ERK/MAPK signaling pathway in secondary hyperparathyroidism (SHPT) rat model. Thirty rats were equally served as the normal and SHPT groups. After transfection, parathyroid cells was assigned into blank, NC, pcDNA3.1‐FGF‐23, siRNA‐FGF‐23, U0126, and siRNA‐FGF‐23 + U0126 groups. The serum levels of Calcium (Ca), Phosphorus (P), alkaline phosphatase (ALP), and PTH were detected. HE and immunohistochemical (IHC) staining were used for the histopathological changes and the FGF‐23, EKR1/2, and pEKR1/2 expressions. qRT‐PCR and Western blotting were performed to determine the mRNA and protein expression of FGF‐23, PTH, MAPK, EKR1/2, and Klotho. The proliferation, apoptosis, and cell cycle were all measured for parathyroid cells by CCK‐8 assay, TUNEL staining and Flow cytometry. Compared with the normal group, the SHPT group showed increased serum levels PTH, P, ALP, and FGF‐23 and mRNA and protein expressions of FGF‐23 and PTH, whereas declined Ca and p‐ERK1/2 expression, mRNA and protein expression of Klotho, cell apoptosis rate was reduced. Furthermore, compared to the blank and NC groups, the pcDNA3.1‐FGF‐23 and U0126 groups had a decreased mRNA expression of Klotho, protein expression of EKR1/2 and Klotho, and cell apoptosis rate was down‐regulated, whereas the RNA and protein expressions of FGF‐23 and PTH were up‐regulated, and cell proliferation was elevated. The opposite results were observed in the siRNA‐FGF‐23 group. Our study demonstrated that FGF‐23 could inhibit signaling transduction of ERK/MAPK pathway and accelerate the secretion of PTH in rats with SHPT.