Fig. 5
From: CFTR dysfunction in smooth muscle drives TGFβ dependent airway hyperreactivity
Despite unchanged baseline pulmonary resistance, Cftrfl/fl; SM-Cre mice treated with TGFβ had elevated AHR linked to increased Smad signaling. A. Baseline pulmonary resistance was unchanged by pulmonary Ad-TGFβ treatment. B. In contrast to baseline resistance, Cftrfl/fl; SM-Cre mice had increased AHR after pulmonary TGFβ exposure. Methacholine challenge testing showed increased AHR in Ad-TGFβ exposed Cftrfl/fl; SM-Cre mice compared to Ad-TGFβ exposed control Cftrfl/fl mice. Box indicates maximal lung resistance values used for linear regression analysis in 4C. *P < 0.05 for area under the curve after 50 mg/mL and 100 mg/mL doses of nebulized methacholine vs Ad-TGFβ exposed control Cftrfl/fl mice by one-way ANOVA with Tukey’s post hoc analysis. C. Linear regression analysis demonstrated a relationship between increased Smad2 signaling, as measured via Western blot analysis, and maximal pulmonary resistance in both Cftrfl/fl and Cftrfl/fl; SM-Cre mice after exposure to pulmonary Ad-TGFβ. Regression line comparison showed a significantly higher y-intercept in Cftrfl/fl; SM-Cre mice, indicating an increased resistance at any given level of Smad2 signaling in the absence of CFTR smooth muscle function. *P < 0.05 versus Ad-TGFβ exposed control Cftrfl/fl mice by ANCOVA analysis. Data are presented as mean ± SD