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Expression of sodium-dependent dicarboxylate transporter 1 (NaDC1/SLC13A2) in
normal and neoplastic human kidney
#MMPMID27927654
Lee HW
; Handlogten ME
; Osis G
; Clapp WL
; Wakefield DN
; Verlander JW
; Weiner ID
Am J Physiol Renal Physiol
2017[Mar]; 312
(3
): F427-F435
PMID27927654
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Regulated dicarboxylate transport is critical for acid-base homeostasis,
prevention of calcium nephrolithiasis, regulation of collecting duct sodium
chloride transport, and the regulation of blood pressure. Although luminal
dicarboxylate reabsorption via NaDC1 (SLC13A2) is believed to be the primary
mechanism regulating renal dicarboxylate transport, the specific localization of
NaDC1 in the human kidney is currently unknown. This study's purpose was to
determine NaDC1's expression in normal and neoplastic human kidneys. Immunoblot
analysis demonstrated NaDC1 expression with an apparent molecular weight of ~61
kDa. Immunohistochemistry showed apical NaDC1 immunolabel in the proximal tubule
of normal human kidney tissue; well-preserved proximal tubule brush border was
clearly labeled. Apical NaDC1 expression was evident throughout the entire
proximal tubule, including the initial proximal convoluted tubule, as identified
by origination from the glomerular tuft, and extending through the terminal of
the proximal tubule, the proximal straight tubule in the outer medulla. We
confirmed proximal tubule localization by colocalization with the proximal tubule
specific protein, NBCe1. NaDC1 immunolabel was not detected other than in the
proximal tubule. In addition, NaDC1 immunolabel was not detected in tumors of
presumed proximal tubule origin, clear cell and papillary renal cell carcinoma,
or in tumors of nonproximal tubule origin, oncocytoma and chromophobe carcinoma.
In summary, 1) in the human kidney, apical NaDC1 immunolabel is present
throughout the entire proximal tubule, and is not detectable in other renal
cells; and 2) NaDC1 immunolabel is not present in renal tumors. These studies
provide important information regarding NaDC1's role in human dicarboxylate
metabolism.
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