The anion transport protein Slc26a9 in the bronchial and intestinal epithelium: Physiological functions, pathophysiological relevance, and interaction with the anion channel CFTR

• Applicant: Professorin Dr. Ursula Seidler
• Subject Area: Gastroenterology ; Anatomy and Physiology
• Term: from 2014 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255182918

Epithelial anion transport has turned out to be of paramount importance for epithelial mucosal protection in all organs studied so far. The Slc26 anion transporter gene family with 10 members plays an important but as yet incompletely understood role in mucosal protective and epithelial transport physiology. Slc26a9 is expressed at high levels in the stomach and the lung, followed by the duodenum, specialized cells in the kidney, the neural system and the reproductive tract. Its transport properties are controversially discussed, and its physiological functions are largely unclear. Recently we could show that Slc26a9-deficient mice loose the ability to secrete gastric acid and develop premalignant lesions in the gastric mucosa. We also found that upon intrabronchial inhalation of IL-13, Slc26a9-deficient mice are not able to upregulate an anion conductance, presumably Slc26a9, and experience bronchial mucus plugging. Polymorphisms in the Slc26a9 gene are associated with an increased risk for meconium ileus in cystic fibrosis patients, neurocognitive defects in schizo¬phrenic patients, and increased risk for childhood asthma. Therefore, we plan to investigate the physiological and pathophysiological role of Slc26a9 in the lung and the small intestine, as well as to study the molecular interaction of Slc26a9 with CFTR. These experiments will provide new insight into the molecular regulation of anion-, fluid and bicarbonate secretion in the airways and the small intestine. They may pave the way for novel drug development strategies for mucolytic and mucosal protective substances for the airways and the duodenum, and result in a better under¬standing of the pathophysiology of epithelial diseases such as obstructive lung disease, peptic ulceration and cystic fibrosis.

• DFG Programme: Research Grants