FIGURE 7.
Inhibition of SYVN1, NEDD8, or FBXO2 partially restores ΔF508-CFTR function in primary CF airway epithelial cells. A, change in It in response to forskolin and IBMX (F&I) treatment in polarized primary airway epithelial cell cultures. n = 4 (minimum) cultures per donor; all treatments were replicated in six donors or more; FBXO2 treatment was replicated in three donors. B, LDH levels measured in the airway surface liquid and basolateral medium of primary air-liquid interface non-CF airway epithelial cultures every 4 days for a period of 28 days post-transfection with the noted reagents. n = 3 donors (three cultures per donor). Error bars indicate S.E. C, cell morphology was assessed by hematoxylin and eosin (H&E) staining and examination of sections of primary non-CF airway epithelial cell cultures at days 14 and 28 post-transfection with the noted interventions. A well differentiated morphology was maintained across all interventions. n = 3 donors (three cultures per donor). A, box and whisker plot (minimum-maximum) represents median. Statistical significance was determined by one-way ANOVA with Holm-Bonferroni correction: *, p < 0.01 (relative to siScr); #, p < 0.01. NoT, no treatment.