Figure 8. In FRT cells, A455E-CFTR functional expression is partially rescued by siRPL12, whereas P67L-CFTR is unaffected.

(A) Following an approximately 30% knockdown of Rpl12, A455E-CFTR band B (black arrowhead) and band C (open arrowhead) are significantly increased (n = 3). (B) A455E-mediated transepithelial ion transport is augmented by Rpl12 depletion (100 nM siRNA, 4 days) and additive to treatment with small molecule correctors (VX-809 or VX-661, 3 μM, 48 hours) (n = 3). (C) P67L-CFTR band C is significantly enhanced as is band B (to a lesser extent) following addition of VX-809 or VX-661 (n = 3). (D) P67L-CFTR ion transport is markedly increased by either CFTR corrector (3 μM, 48 hours), yet unaltered by siRPL12 (100 nM, 4 days) (n = 3). Representative measurements in left panels are quantified on right. Data shown in A and C are represented as mean ± SEM normalized to NS siRNA without drug treatment (dotted line set to 100%). Asterisks represent statistical comparison versus NS siRNA without pharmacocorrection. *P < 0.0167; **P < 0.01; ***P < 0.001; ****P < 0.0001, unequal variance t test on log₂-transformed data with post-hoc Bonferroni’s correction; α = 0.0167. Data shown in B and D are represented as mean ± SEM. Asterisks represent forskolin+VX-770 stimulation (i.e., total constitutive plus activated CFTR function) versus NS siRNA without drug treatment. *P < 0.00625; **P < 0.001; ***P < 0.0001, unequal variance t test with post-hoc Bonferroni’s correction; α = 0.00625. VX-809 or VX-661 augmented A455E-CFTR band C (P < 0.01) and activity (P < 0.001) above siRPL12 alone. Forskolin, 5 μM; genistein, 50 μM; Inh₁₇₂, 10 μM.