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. 2022 Feb 1;132(3):e146926. doi: 10.1172/JCI146926

Figure 10. The effects of Smad7 on fibroblast activity are mediated, at least in part, through an interaction with ErbB1/2.

Figure 10

Comparison of the effects of the dual ErbB1/2 inhibitor lapatinib (Inh) on extracellular matrix gene expression in Smad7-KO and WT fibroblasts, in the presence or absence of amphiregulin. (A–J) Unstimulated cardiac fibroblasts (first 4 bars of each graph): ErbB1/2 inhibition in unstimulated cardiac fibroblasts abrogates the effects of Smad7 loss on expression of Adamts1, Adamts2, Mmp12, and Mmp14 (proteases); Itga2, Itga3, and Itgb1 (integrins); Tsp3 (matricellular protein); and Cd44 and Vcam-1 (adhesion molecules), without exerting any effects on WT cells. Amphiregulin-stimulated cardiac fibroblasts (last 4 bars of each graph): In the presence of amphiregulin, the effects of Smad7 loss on Cd44, Itga2, Itgb1, and Mmp12 synthesis are accentuated. ErbB1/2 inhibition markedly attenuates the effects of Smad7 loss. Statistical comparison (A–J) was performed using 1-way ANOVA followed by Tukey’s multiple comparison test (n = 3). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; ^P < 0.05, ^^P < 0.01, ^^^P < 0.001, ^^^^P < 0.0001 vs. corresponding WT; ##P < 0.01, ###P < 0.001, ####P < 0.0001 vs. unstimulated.