Figure 5. Smad7 loss accentuates synthesis of structural and matricellular genes by cardiac fibroblasts and modulates expression of MMPs and TIMPs.

Expression of extracellular matrix genes was assessed using a PCR array and was compared between Smad7-KO fibroblasts (S7 KO, induced through overexpression of adeno-Cre in Smad7^fl/fl cells) and control fibroblasts (Smad7^fl/fl). (A–H) Smad7 loss accentuates fibroblast expression of genes encoding structural matrix proteins, including collagen type I α1, collagen type III α1, collagen type V α1, collagen type VI α1, and fibronectin, and matricellular proteins, such as periostin, thrombospondin 1, and thrombospondin 2. (I–L) Smad7 also modulates expression of genes associated with matrix remodeling, such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs). Smad7-KO cells have lower expression of Mmp1α, but markedly higher expression of Mmp3, Timp1, and Timp2. Comparisons between 2 groups (A–L) was performed by unpaired, 2-tailed Student’s t test with Welch’s correction for unequal variances (n = 3/group). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.