Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients

被引：195

作者：

Komaba, Hirotaka ^{[1
,2
]}

Goto, Shunsuke ^{[1
,2
]}

Fujii, Hideki ^{[1
,2
]}

Hamada, Yasuhiro ^{[1
,2
]}

Kobayashi, Akira ^{[3
]}

Shibuya, Koji ^{[4
]}

Tominaga, Yoshihiro ^{[5
]}

Otsuki, Naoki ^{[6
]}

Nibu, Ken-ichi ^{[6
]}

Nakagawa, Kimie ^{[7
]}

Tsugawa, Naoko ^{[7
]}

Okano, Toshio ^{[7
]}

Kitazawa, Riko ^{[8
]}

Fukagawa, Masafumi ^{[1
,2
]}

机构：

[1] Kobe Univ, Sch Med, Div Nephrol, Kobe, Hyogo 650, Japan

[2] Kobe Univ, Sch Med, Kidney Ctr, Kobe, Hyogo 650, Japan

[3] Kobayashi Clin, Kobe, Hyogo, Japan

[4] Sumiyoshigawa Hosp, Kobe, Hyogo, Japan

[5] Nagoya Second Red Cross Hosp, Dept Transplant & Endocrine Surg, Nagoya, Aichi, Japan

[6] Kobe Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Kobe, Hyogo 650, Japan

[7] Kobe Pharmaceut Univ, Dept Hyg Sci, Kobe, Hyogo 658, Japan

[8] Kobe Univ, Sch Med, Div Pathol, Kobe, Hyogo 650, Japan

来源：

KIDNEY INTERNATIONAL | 2010年 / 77卷 / 03期

关键词：

chronic kidney disease; FGF23; FGFR1; Klotho; parathyroid; secondary hyperparathyroidism; FIBROBLAST GROWTH FACTOR-23; CHRONIC KIDNEY-DISEASE; ADVANCED SECONDARY HYPERPARATHYROIDISM; CHRONIC-RENAL-FAILURE; VITAMIN-D METABOLISM; DIALYSIS PATIENTS; CALCIUM RECEPTOR; IN-VITRO; CIRCULATING FIBROBLAST-GROWTH-FACTOR-23; CALCITRIOL THERAPY;

D O I：

10.1038/ki.2009.414

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Fibroblast growth factor 23 (FGF23) exerts its effect by binding to its cognate FGF receptor 1 (FGFR1) in the presence of its co-receptor Klotho. Parathyroid glands express both FGFR1 and Klotho, and FGF23 decreases parathyroid hormone gene expression and hormone secretion directly. In uremic patients with secondary hyperparathyroidism (SHPT), however, parathyroid hormone secretion remains elevated despite extremely high FGF23 levels. To determine the mechanism of this resistance, we measured the expression of Klotho, FGFR1, and the proliferative marker Ki67 in 7 normal and 80 hyperplastic parathyroid glands from uremic patients by immunohistochemistry. All uremic patients had severe SHPT along with markedly high FGF23 levels. Quantitative real-time reverse transcription PCR showed that the mRNA levels for Klotho and FGFR1 correlated significantly with their semi-quantitative immunohistochemical intensity. Compared with normal tissue, the immunohistochemical expression of Klotho and FGFR1 decreased, but Ki67 expression increased significantly in hyperplastic parathyroid glands, particularly in glands with nodular hyperplasia. These results suggest that the depressed expression of the Klotho-FGFR1 complex in hyperplastic glands underlies the pathogenesis of SHPT and its resistance to extremely high FGF23 levels in uremic patients. Kidney International (2010) 77, 232-238; doi:10.1038/ki.2009.414; published online 4 November 2009

引用

页码：232 / 238

页数：7

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