Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease

被引：175

作者：

Galitzer, H. ^{[1
]}

Ben-Dov, I. Z. ^{[1
]}

Silver, Justin ^{[1
]}

Naveh-Many, Tally ^{[1
]}

机构：

[1] Hadassah Hebrew Univ, Dept Nephrol, Med Ctr, Jerusalem, Israel

来源：

KIDNEY INTERNATIONAL | 2010年 / 77卷 / 03期

基金：

以色列科学基金会;

关键词：

chronic renal failure; gene expression; hyperparathyroidism; parathyroid hormone; RENAL-FAILURE; VITAMIN-D; EXPRESSION; RECEPTOR; RATS; FIBROBLAST-GROWTH-FACTOR-23; CALCIUM; KLOTHO; FGF23; HEMODIALYSIS;

D O I：

10.1038/ki.2009.464

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：

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

引用

页码：211 / 218

页数：8

共 24 条

[1] The parathyroid is a target organ for FGF23 in rats [J].

Ben-Dov, Iddo Z. ;

Galitzer, Hillel ;

Lavi-Moshayoff, Vardit ;

Goetz, Regina ;

Kuro-o, Makoto ;

Mohammadi, Moosa ;

Sirkis, Roy ;

Naveh-Many, Tally ;

Silver, Justin .

JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (12) :4003-4008

[2] Type I membrane Klotho expression is decreased and inversely correlated to serum calcium in primary hyperparathyroidism [J].

Bjorklund, Peyman ;

Krajisnik, Tijana ;

Akerstrom, Goran ;

Westin, Gunnar ;

Larsson, Tobias E. .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (10) :4152-4157

[3] Phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure [J].

Denda, M ;

Finch, J ;

Slatopolsky, E .

AMERICAN JOURNAL OF KIDNEY DISEASES, 1996, 28 (04) :596-602

[4] Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: The mild to moderate kidney disease (MMKD) study [J].

Fliser, Danilo ;

Kollerits, Barbara ;

Neyer, Ulrich ;

Ankerst, Donna P. ;

Lhotta, Karl ;

Lingenhel, Arno ;

Ritz, Eberhard ;

Kronenberg, Florian .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (09) :2600-2608

[5] DECREASED 1,25-DIHYDROXYVITAMIN-D(3) RECEPTOR DENSITY IS ASSOCIATED WITH A MORE SEVERE FORM OF PARATHYROID HYPERPLASIA IN CHRONIC UREMIC PATIENTS [J].

FUKUDA, N ;

TANAKA, H ;

TOMINAGA, Y ;

FUKAGAWA, M ;

KUROKAWA, K ;

SEINO, Y .

JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (03) :1436-1443

[6] REACCUMULATION OF THYROGLOBULIN AND COLLOID IN RAT AND MOUSE THYROID-FOLLICLES DURING INTENSE THYROTROPIN STIMULATION - A CLUE TO THE PATHOGENESIS OF COLLOID GOITERS [J].

GERBER, H ;

STUDER, H ;

CONTI, A ;

ENGLER, H ;

KOHLER, H ;

HAEBERLI, A .

JOURNAL OF CLINICAL INVESTIGATION, 1981, 68 (05) :1338-1347

[7] Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism [J].

Gogusev, J ;

Duchambon, P ;

Hory, B ;

Giovannini, M ;

Goureau, Y ;

Sarfati, E ;

Drueke, TB .

KIDNEY INTERNATIONAL, 1997, 51 (01) :328-336

[8] Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease [J].

Gutierrez, O ;

Isakova, T ;

Rhee, E ;

Shah, A ;

Holmes, J ;

Collerone, G ;

Jüppner, H ;

Wolf, M .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2005, 16 (07) :2205-2215

[9] Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis [J].

Gutierrez, Orlando M. ;

Mannstadt, Michael ;

Isakova, Tamara ;

Rauh-Hain, Jose Alejandro ;

Tamez, Hector ;

Shah, Anand ;

Smith, Kelsey ;

Lee, Hang ;

Thadhani, Ravi ;

Juppner, Harald ;

Wolf, Myles .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (06) :584-592

[10] Parallel reduction of pancreas insulin content and insulin secretion in 48-h tolbutamide-infused normoglycemic rats [J].

Hosokawa, YA ;

Leahy, JL .

DIABETES, 1997, 46 (05) :808-813

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