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Iodine and the Body

Kidney

• Bakheet, Hammami
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• Zhou

   

Spitzweg

Expression of the sodium iodide symporter in human kidney.

Spitzweg C, Dutton CM, Castro MR, Bergert ER, Goellner JR, Heufelder AE, Morris JC.

Kidney Int. 2001 Mar;59(3):1013-23.

"BACKGROUND: The human sodium iodide symporter (hNIS) is a transmembrane protein that mediates the active transport of iodide in the thyroid gland. Following cloning of NIS, NIS expression has been detected in a broad range of nonthyroidal tissues, suggesting that iodide transport in these tissues is conferred by the expression of functional NIS protein.

METHODS: The aim of this study was to examine functional hNIS expression in kidney by reverse transcription-polymerase chain reaction (RT-PCR), ribonuclease protection assay (RPA), immunohistochemistry, and Western blot analysis accompanied by iodide accumulation studies in kidney cells.

RESULTS: Using a pair of full-length hNIS-specific oligonucleotide primers, RT-PCR followed by Southern hybridization revealed hNIS mRNA expression in normal human kidney tissue. The PCR products were subjected to automated sequencing and revealed full identity with the published human thyroid-derived NIS cDNA sequence. Furthermore, positive protected bands indicating the presence of hNIS mRNA were apparent in RPA gel lanes corresponding to human kidney cells as well as Chinese hamster ovary (CHO) cells stably transfected with hNIS cDNA and Graves' thyroid tissue. Immunohistochemical analysis of normal human kidney tissue using a mouse monoclonal hNIS-specific antibody showed marked hNIS-specific immunoreactivity confined to tubular cells, while no hNIS-specific immunoreactivity was detected in the glomeruli. NIS protein expression in human kidney cells was further confirmed by Western blot analysis. In addition, accumulation of (125)I was detected in human kidney cells in vitro and was shown to be sodium dependent and sensitive to perchlorate.

CONCLUSIONS: Functional hNIS expression was demonstrated in the renal tubular system, suggesting that renal iodide transport may be, at least in part, an active process driven by NIS."
 

"We found most prominent hNIS-specific immunoreactivity in the distal tubular system, with lower staining in the proximal tubules and no hNIS-specific immunostaining in the glomeruli."

"Possible functions of trapped and organified iodide in extrathyroidal tissues may include antiproliferative and antioxidative effects, as demonstrated for certain iodolipids (iodolactones, iodoaldehydes) in the thyroid gland.  Interestingly, alpha-iodohexadecanal, a naturally occurring iodoaldehyde has been shown to inhibit adenylyl cyclase in kidney cortex in a similar fashion to its activity in thyroid cells."

"Iodide is subject to an active secretory process by the renal tubule."

"It has been postulated that iodide enters the basolateral aspect of the cell through the Na/K/2Cl cotransporter and exits the cell via the apical CFTR (cystic fibrosis transmembrane regulator) chloride channel, thereby mediating the active transcellular secretion of iodide into the cyst lumen.... It is likely that hNIS is responsible for the secretion of I-131 into renal cysts and therefore iodide transport in the renal tubular system.... NIS protein expression in membrane preparations of human kidney cells, detection of NIS-specific iodide accumulating activity in human kidney cells..., cytoplasmic NIS-specific immunoreactivity throughout the proximal and distal tubular system, including collecting ducts and the thick ascending loop of Henle suggest that NIS may mediate transepithelial as well as intracellular iodide transport in kidney."

"Iodide clearance in the kidney varies with thyroid status, being lower in hypothyroidism and increased in hyperthyroidism, which is mainly explained by parallel changes of glomerular filtration.  Given the expression of functional NIS protein in the renal tubular system, it also may be possible that NIS protein expression or functional NIS activity is regulated in altered thyroid status to adjust iodide clearance.... Goiter formation, in iodine deficient areas may result, at least in part, from interindividual variability of renal NIS expression levels."

"End-stage renal disease patients have been reported to have a higher frequency of goiter, thyroid nodules, and hypothyroidism.  Primary hypothyroidism occurs in up to 9.5% of end-stage renal disease patients compared with 0.6 to 1/1% of the general population, with elevated antimicrosomal antibody titers in about 50%, suggesting an underlying autoimmune mechanism."

"hNIS, which has been identified as a new potential autoantigen in the pathogenesis of autoimmune thyroid disease, may become a target antigen for cross-reacting T cells and autoantibodies during the evolution of chronic renal disease, thereby eliciting an autoimmune process in the thyroid gland."

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