TGF-beta downregulation of VX-809-corrected F508del CFTR in HAECs.

<p>F508del CFTR homozygous HAECs were grown at air-liquid interface culture for 6 weeks and treated with TGF-beta (10 ng/ml) and/or VX-809 (3 µM) for 48 h prior to I_sc measurement. (<b>A</b>) Stimulated I_sc under control (left), VX-809 alone (middle), or VX-809 + TGF-beta (right) treatment conditions. *<i>P</i><0.035, VX-809 compared with either control or VX-809 + TGF-beta. (<b>B</b>) Lysates of F508del HAECs from each filter were prepared and subjected to PAGE and immunoblot as described in Methods for detection of B Band and C Band under control, VX-809 alone, or VX-809 + TGF-beta treatment conditions. (<b>C</b>) All tested doses of TGF-beta downregulated VX-809-corrected F508del CFTR. *<i>P</i><0.00017, VX-809 compared with untreated control; **<i>P</i><0.0001, 0.1 ng TGF-beta + VX-809 compared with VX-809 alone. ***<i>P</i><0.0001, 1 ng TGF-beta + VX-809 compared with VX-809 alone. ****<i>P</i><0.0001, 10 ng TGF-beta + VX-809 compared with VX-809 alone. (<b>D</b>) Summary densitometry data for detection of F508del CFTR B Band (left) and C Band (right) with and without TGF-beta (10 ng/ml, similar to 5B). *<i>P</i>≤0.047, B Band VX-809 compared with either control or VX-809 + TGF-beta. *<i>P</i>≤0.05, C Band VX-809 compared with either control or VX-809 + TGF-beta.