Human Nasal and Bronchial Epithelium in Cystic Fibrosis: Differences in Expression of Airway pH Regulatory Proteins

作者：Davis MD, Smith L, Zhao Y, Rahman RA, Khalid F, Chmiel J, Boyne K, Daniels IA, Gaston B, Marozkina N · 发表于：Pediatric pulmonology · 年份：2026 · DOI：10.1002/ppul.71784 · 被引用次数：40 · 研究领域：Cystic Fibrosis、Nasal Mucosa、Bronchi、Respiratory Mucosa、Humans、Hydrogen-Ion Concentration、Carbonic Anhydrases、NADPH Oxidases、Cells, Cultured、Female、Male、NADPH Oxidase 2

BACKGROUND: Decreased apical bicarbonate transport into the airway surface liquid (ASL) has been associated with decreased ASL pH, which can have adverse respiratory effects. However, the human CF epithelium can normalize ASL pH. Thus, we hypothesized that pH regulatory proteins other than the CFTR could be altered in the CF epithelium. METHODS: Primary human nasal and bronchial epithelial cells from healthy controls and CF subjects were grown at air-liquid interface until fully ciliated. Western blot was used to measure proteins known to affect human epithelial pH: carbonic anhydrases (CA) 1, 2, and 12; voltage-gated proton channel (Hv1); lactate dehydrogenases (LDH) A, B, D; dual oxidases (DUOX) 1, 2; Na+/H+ exchange regulatory factor; potassium-transporting ATPase alpha chain 2 (ATP12A), S-nitrosoglutathione reductase (GSNOR); glutaminase; vacuolar-type ATPase (VTP-ase); and NADPH oxidases (NOX) 1-4. RESULTS: NOX2 was decreased in CF nasal epithelial cells compared to controls. CA1, CA2, CA12, Hv1, LDHA, LDHD, ATP12A, GSNOR and NOX4 expression were increased in CF bronchial epithelial cells relative to the controls. Beta actin expression was variable, making normalization challenging. CONCLUSIONS: Expression of CA's, Hv1, LDH's, ATP12A, GSNOR, and NOX4 were generally increased in bronchial epithelium from patients with CF. These proteins could serve to normalize the CF epithelial pH. Nasal cells did not have these changes, arguing that findings from primary nasal cells ...