Contributions of the anion exchangers SLC26A1 , SLC26A2 , SLC26A3 , and SLC26A6 to intestinal oxalate transport in human Caco2‐ BBE cells

Abstract Kidney stones affect ~1 in 5 men and 1 in 11 women, with 70%–80% being composed of calcium oxalate. Knowing the contributions of anion exchangers SLC26A2 (A2), A3, and A6 to apical and A1 to basolateral oxalate transport in human intestinal Caco2‐BBE (C2) cells is important since enhancing intestinal oxalate secretion (A6/2/?A1) and reducing intestinal oxalate absorption (A3) are potential therapeutic targets. We previously showed A6 contributes > A2 to oxalate transport in C2 cells. Here, we report the contributions of combined A2+A6, A1, and A3 to oxalate transport in C2 cells using siRNA knockdown. A2 (74% reduced mRNA expression), A6 (64% reduced protein abundance), and A2+A6 (combined knockdown utilizing same A2 or A6 C2 silencing batches) mediate 31.1%, 57%, and 78% of apical oxalate transport, respectively. A1 mediates 30.9% (59.5% reduced protein abundance) of basolateral oxalate transport. A3 (78.7% reduced protein abundance) has no significant contribution to apical oxalate transport. In conclusion, most apical oxalate transport in C2 cells is mediated by A2+A6 (with no significant contribution from A3) while A1 contributes to basolateral oxalate transport. Thus, C2 cells can be used for screening/testing novel drugs targeting these transporters, which will have significant potential therapeutic implications for oxalate‐related disorders.