Pendrin is an
anion exchanger whose mutations are known to cause
hearing loss. However, recent data support the linkage between pendrin expression and airway diseases, such as
asthma. To evaluate the role of pendrin in the regulation of the airway surface liquid (ASL) volume and
mucin expression, we investigated the function and expression of pendrin and
ion channels and
anion exchangers. Human nasal epithelial cells were cultured from 16 deaf patients carrying pendrin mutations (DFNB4) and 17 controls. The cells were treated with
IL-13 to induce mucus hypersecretion. Airway surface liquid thickness was measured and real-time polymerase chain reaction was performed targeting various transporters and MUC5AC.
Anion exchanger activity was measured using a pH-sensitive
fluorescent probe.
Periodic acid-Schiff staining was performed on the cultured cells and inferior turbinate tissues. The ASL layer of the nasal epithelia from DFNB4 subjects was thicker than the controls, and the difference became more prominent following
IL-13 stimulation. There was no difference in
anion exchange activity after
IL-13 treatment in the cells from DFNB4 patients, while it increased in the controls. Goblet cell
metaplasia induced by
IL-13 treatment seen in the controls was not observed in the DFNB4 cells. Furthermore, the
periodic acid-Schiff staining-positive area was lesser in the inferior turbinate tissues from DFNB4 patients that those from controls. Pendrin plays a critical role in ASL volume regulation and
mucin expression as pendrin-deficient airway epithelial cells are refractory to stimulation with
IL-13. Specific blockers targeting pendrin in the airways may therefore have therapeutic potential in the treatment of allergic airway diseases.