title: Thick airway surface liquid volume and weak mucin expression in pendrin-deficient human airway epithelia.
abstract: 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.
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea Research Center for Human Natural Defense System, Yonsei University, Seoul, Korea Department of Otorhinolaryngology, Yonsei University, Seoul, Korea.
authors.forename: Hyun Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Research Center for Human Natural Defense System, Yonsei University, Seoul, Korea Department of Otorhinolaryngology, Yonsei University, Seoul, Korea.
authors.forename: Jee Eun
authors.initials: JE
authors.lastname: Yoo
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences Yonsei University, Incheon, Korea.
authors.forename: Wan
authors.initials: W
authors.lastname: Namkung
authors.affiliation: Department of Otorhinolaryngology, Yonsei University, Seoul, Korea Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyung-Ju
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
authors.forename: Kyubo
authors.initials: K
authors.lastname: Kim
authors.affiliation: Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joo Wan
authors.initials: JW
authors.lastname: Kang
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea Research Center for Human Natural Defense System, Yonsei University, Seoul, Korea Department of Otorhinolaryngology, Yonsei University, Seoul, Korea Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea Research Center for Human Natural Defense System, Yonsei University, Seoul, Korea Department of Otorhinolaryngology, Yonsei University, Seoul, Korea Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea jychoi@yuhs.ac.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
keywords: SLC26A4; anion channel; asthma