ABSTRACT

SLC26A9 is one out of 11 proteins that belong to the SLC26A family of anion transporters. Apart from expression in the gastrointestinal tract, SLC26A9 is also found in the respiratory system, in male tissues and in the skin. SLC26A9 has gained attention because of its modifier role in the gastrointestinal manifestation of cystic fibrosis (CF). SLC26A9 appears to have an impact on the extent of intestinal obstruction caused by meconium ileus. SLC26A9 supports duodenal bicarbonate secretion, but was assumed to provide a basal Cl- secretory pathway in airways. However, recent results show that basal airway Cl- secretion is due to cystic fibrosis conductance regulator (CFTR), while SLC26A9 may rather secrete HCO₃-, thereby maintaining proper airway surface liquid (ASL) pH. Moreover, SLC26A9 does not secrete but probably supports reabsorption of fluid particularly in the alveolar space, which explains early death by neonatal distress in Slc26a9-knockout animals. While the novel SLC26A9 inhibitor S9-A13 helped to unmask the role of SLC26A9 in the airways, it also provided evidence for an additional role in acid secretion by gastric parietal cells. Here we discuss recent data on the function of SLC26A9 in airways and gut, and how S9-A13 may be useful in unraveling the physiological role of SLC26A9.

摘要

SLC26A9 是属于阴离子转运蛋白 SLC26A 家族的 11 种蛋白质之一。除了在胃肠道中表达外，SLC26A9 还存在于呼吸系统、男性组织和皮肤中。SLC26A9 因其在囊性纤维化 (CF) 的胃肠道表现中的修饰作用而受到关注。SLC26A9 似乎对胎粪性肠梗阻引起的肠梗阻程度有影响。SLC26A9 支持十二指肠碳酸氢盐分泌，但被认为在气道中提供基础 Cl- 分泌途径。然而，最近的结果表明，基础气道 Cl- 分泌是由于囊性纤维化传导调节剂 (CFTR)，而 SLC26A9 可能更愿意分泌 HCO ₃-，从而保持适当的气道表面液体 (ASL) pH 值。此外，SLC26A9 不分泌但可能支持液体的重吸收，特别是在肺泡腔中，这解释了 Slc26a9 基因敲除动物因新生儿窘迫而过早死亡的原因。虽然新型 SLC26A9 抑制剂 S9-A13 有助于揭示 SLC26A9 在气道中的作用，但它也为胃壁细胞在酸分泌中的额外作用提供了证据。在这里，我们讨论了有关 SLC26A9 在气道和肠道中的功能的最新数据，以及 S9-A13 如何有助于揭示 SLC26A9 的生理作用。