Fibroblast growth factor 23 is upregulated in the kidney in a chronic kidney disease rat model.
Fibroblast growth factor 23 is upregulated in the kidney in a chronic kidney disease rat model.
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DOI：
10.1371/journal.pone.0191706
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Tsuchiya K
中科院分区：
文献类型：
--
作者：
Sugiura H;Matsushita A;Futaya M;Teraoka A;Akiyama KI;Usui N;Nagano N;Nitta K;Tsuchiya K
激素成纤维细胞生长因子23（FGF 23）由骨分泌并参与磷（P）代谢。FGF 23主要结合FGF受体，FGF受体与肾脏或甲状旁腺中的αKlotho相互作用，并调节钠依赖性磷酸盐协同转运蛋白IIa型（NaPi-IIa）和IIc型（NaPi-IIc）表达、1，25-二羟基维生素D3（1，25（OH）2D 3）活性和甲状旁腺激素（PTH）分泌。在这项研究中，我们利用半肾切除大鼠喂养高磷饮食（HP Nx），大鼠进行部分肾切除术（PN）和大鼠阿霉素诱导的肾功能衰竭（DXR）作为慢性肾脏疾病（CKD）的动物模型，并分析P代谢和FGF 23在肾脏中的表达在每个CKD模型。本研究采用高浓度P、1，25（OH）_2D_3和转化生长因子β_1（TGFβ_1）对HK_2细胞进行体外培养，观察其对FGF_23表达的影响。在HP Nx和PN大鼠中，血液FGF 23和PTH水平均升高。而1，25（OH）_2D_3在HP Nx大鼠中升高，在PN大鼠中降低。3种动物模型中，肾脏αKlotho、NaPi-IIa和NaPi-IIc的mRNA表达均降低，TGFβ1、胶原1a 1、骨桥蛋白和FGF 23的mRNA表达均升高。FGF 23蛋白和mRNA在HP和PN大鼠的延伸小管上皮中高水平表达，这是骨桥蛋白阳性区域。在与TGFβ1孵育的HK 2细胞中，FGF 23和骨桥蛋白mRNA表达;然而，在体外与1，25（OH）2D 3和高P水平孵育的HK 2细胞中，这些水平没有改变。总之，FGF 23在CKD模型大鼠的肾脏中表达。在用TGFβ1刺激后，强烈怀疑损伤的肾小管上皮细胞表达FGF 23和骨桥蛋白。肾脏中产生的FGF 23可能有助于CKD患者的P代谢。
The hormone fibroblast growth factor 23 (FGF23) is secreted from bone and is involved in phosphorus (P) metabolism. FGF23 mainly binds the FGF receptor, which interacts with αKlotho in the kidney or parathyroid and regulates Na-dependent phosphate co-transporter type IIa (NaPi-IIa) and type IIc (NaPi-IIc) expression, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) activity, and parathyroid hormone (PTH) secretion. In this study, we utilized hemi-nephrectomized rats fed a high-P diet (HP Nx), rats subjected to a partial nephrectomy (PN) and rats with doxorubicin-induced renal failure (DXR) as chronic kidney disease (CKD) animal models and analyzed the P metabolism and FGF23 expression in the kidneys in each CKD model. We cultured HK2 cells with a high level of P, 1,25(OH)2D3 or transforming growth factor-β1 (TGFβ1) to investigate the FGF23 expression mechanism. In both the HP Nx and PN rats, the blood FGF23 and PTH levels were increased. However, the 1,25(OH)2D3 level was increased in the HP Nx rats and decreased in the PN rats. In all three animal models, the mRNA expression of αKlotho, NaPi-IIa and NaPi-IIc was decreased, and the mRNA expression of TGFβ1, collagen1a1, osteopontin and FGF23 was elevated in the kidney. FGF23 protein and mRNA were expressed at high levels in the extended tubule epithelium, which was an osteopontin-positive region in the HP and PN rats. FGF23 and osteopontin mRNAs were expressed in HK2 cells incubated with TGFβ1; however, these levels were not altered in HK2 cells incubated with 1,25(OH)2D3 and high P levels in vitro. Altogether, FGF23 is expressed in the kidneys in CKD model rats. Following stimulation with TGFβ1, the injured renal tubular epithelial cells are strongly suspected to express both FGF23 and osteopontin. FGF23 produced in the kidney might contribute to P metabolism in subjects with CKD.
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影响因子：
33.6
作者：
Martin A;David V;Quarles LD
通讯作者：
Quarles LD
影响因子：
3.7
作者：
Sakan H;Nakatani K;Asai O;Imura A;Tanaka T;Yoshimoto S;Iwamoto N;Kurumatani N;Iwano M;Nabeshima Y;Konishi N;Saito Y
通讯作者：
Saito Y
DOI：
10.1056/nejmoa0706130
发表时间：
2008-08-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Gutiérrez OM;Mannstadt M;Isakova T;Rauh-Hain JA;Tamez H;Shah A;Smith K;Lee H;Thadhani R;Jüppner H;Wolf M
通讯作者：
Wolf M
影响因子：
13.6
作者：
Olauson, Hannes;Lindberg, Karolina;Larsson, Tobias E.
通讯作者：
Larsson, Tobias E.
影响因子：
13.6
作者：
Rodriguez-Ortiz, Maria E.;Lopez, Ignacio;Almaden, Yolanda
通讯作者：
Almaden, Yolanda