High-mobility group box-1 protein (HMGB-1)-receptor for advanced glycation end products (RAGE) axis plays an important role in regulating transepithelial Na+ transport. A, top: normal small airway epithelial cells (SAECs) after 3 days under air-liquid interface and on permeable support culture system. A, bottom: culture of confluent normal SAECs on permeable support (10 days) allows for measurement of transepithelial resistance (RTE) and calculation of equivalent short-circuit current (Isc). B and C: SAEC RTE and equivalent Isc values following application of HMGB-1 (0.5 μg/mL, n = 8) and HMGB-1 + FPS-ZM1 (1 μM, n = 7). Amiloride (amil, 1 μM, n = 5) treatments were conducted separately, as indicated by //. FPS-ZM1 pretreatment attenuates HMGB-1-mediated increase in Isc. *P < 0.05, HMGB-1 vs. HMGB-1 + FPS-ZM1 (by paired t test). #P < 0.05 vs. respective control treatment group (t = 0 min) (by repeated-measures ANOVA followed by post hoc Holm’s t test).