Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease
Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease
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DOI：
10.1038/ki.2009.464
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发表时间：
2010-02-01
影响因子：
19.6
通讯作者：
Naveh-Many, Tally
中科院分区：
文献类型：
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作者：
Galitzer, H.;Ben-Dov, I. Z.;Naveh-Many, Tally
虽然成纤维细胞生长因子23（FGF 23）通过其受体Klotho-FGFR 1c作用降低甲状旁腺激素表达，但尽管血清FGF 23升高，这种激素在慢性肾病中仍增加。我们测量了可能的因素，可能有助于抵抗甲状旁腺FGF 23在大鼠与饮食腺嘌呤诱导的慢性肾脏疾病模型。定量免疫组织化学和逆转录-PCR分析，激光捕获显微镜显示，Klotho和FGFR 1蛋白和mRNA水平下降，在组织切片的甲状旁腺。重组FGF 23未能降低血清甲状旁腺激素水平或激活晚期实验性慢性肾病大鼠腺体中的丝裂原活化蛋白激酶信号通路。在甲状旁腺器官培养中，FGF 23的加入降低了对照动物或患有早期但非晚期慢性肾病的大鼠的甲状旁腺激素分泌和mRNA水平。我们的研究结果表明，由于Klotho-FGFR 1c受体复合物的下调，在已建立的慢性肾脏疾病中，循环FGF 23的增加不会降低甲状旁腺激素水平。这种体内抗性在体外甲状旁腺器官培养中持续存在。Kidney International（2010）77，211-218; doi：10.1038/ki.2009.464; 2009年12月16日在线发表
Although fibroblast growth factor 23 (FGF23) acting through its receptor Klotho-FGFR1c decreases parathyroid hormone expression, this hormone is increased in chronic kidney disease despite an elevated serum FGF23. We measured possible factors that might contribute to the resistance of parathyroid glands to FGF23 in rats with the dietary adenine-induced model of chronic kidney disease. Quantitative immunohistochemical and reverse transcription-PCR analysis using laser capture microscopy showed that both Klotho and FGFR1 protein and mRNA levels were decreased in histological sections of the parathyroid glands. Recombinant FGF23 failed to decrease serum parathyroid hormone levels or activate the mitogen-activated protein kinase signaling pathway in the glands of rats with advanced experimental chronic kidney disease. In parathyroid gland organ culture, the addition of FGF23 decreased parathyroid hormone secretion and mRNA levels in control animals or rats with early but not advanced chronic kidney disease. Our results show that because of a downregulation of the Klotho-FGFR1c receptor complex, an increase of circulating FGF23 does not decrease parathyroid hormone levels in established chronic kidney disease. This in vivo resistance is sustained in parathyroid organ culture in vitro. Kidney International (2010) 77, 211-218; doi:10.1038/ki.2009.464; published online 16 December 2009