Cell Biology – Immunology – Pathology

Kidney International (1998) 54, 1150–1156; doi:10.1046/j.1523-1755.1998.00117.x

Dietary salt regulates expression of Tamm-Horsfall glycoprotein in rats

Wei-Zhong Ying and Paul W Sanders

Nephrology Research and Training Center, Comprehensive Cancer Center, and Cell Adhesion and Matrix Research Center, Division of Nephrology, Department of Medicine and Department of Physiology & Biophysics, University of Alabama at Birmingham, and Department of Veterans Affairs Medical Center, Birmingham, Alabama, USA

Correspondence: Paul W. Sanders, M.D., Division of Nephrology/Department of Medicine, 642 Lyons-Harrison Research Building, University of Alabama at Birmingham, Birmingham, Alabama 35294-0007, USA. E-mail: paul_sanders@nrtc.dom.uab.edu

Received 4 March 1998; Revised 11 May 1998; Accepted 11 May 1998.

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Abstract

Dietary salt regulates expression of Tamm-Horsfall glycoprotein in rats.

Background

 

Tamm-Horsfall glycoprotein (THP) is a unique protein that is produced exclusively by cells of the thick ascending limb of Henle's loop (TALH). This study examined whether dietary salt altered renal THP production.

Methods

 

Male Sprague-Dawley rats were examined on days 1, 4, and 15 following placement in metabolic cages on diet that contained 0.3%, 1.0% or 8.0% NaCl. THP expression was quantified using Northern hybridization and Western blotting analysis.

Results

 

An increase in dietary salt produced sustained increases in relative steady-state mRNA and protein levels of THP in the kidney. Addition of furosemide, but not chlorothiazide, to animals on the 8.0% NaCl diet further augmented steady-state mRNA levels of THP.

Conclusions

 

An increase in dietary salt and the loop diuretic, furosemide, increased expression of THP in the rat. The data support the involvement of this unique protein in the function of the TALH during changes in dietary salt. These findings also suggest that restriction of dietary salt may be beneficial in cast nephropathy in multiple myeloma and recurrent nephrolithiasis, two diseases in which THP can play an important pathogenetic role.

Keywords:

uromodulin, thick ascending limb of the loop of Henle, furosemide, chlorothiazide, gene expression

Abbreviations:

GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Hi-C, animals maintained on 8.0% NaCl chow and given chlorothiazide; Hi-F, animals maintained on 8.0% NaCl chow and given furosemide; Hi-salt, animals maintained on 8.0% NaCl chow; Lo-salt, animals maintained on 0.3% NaCl chow; Mid-salt, animals maintained on 1.0% NaCl chow; TALH, thick ascending limb of the loop of Henle; THP, Tamm-Horsfall glycoprotein

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