NOD1 activation increases cardiac fibrosis and TGF-β pathway in hearts isolated from iE treated mice.

<p>(A) Histological analysis of the hearts from mice treated with vehicle (Veh.), with 150 µg of iEDAP (iE) or with 150 µg of iE-Lys (NOD1 inactive analogue of iEDAP). Representative whole-heart cross-sections are shown (magnification x20). Myocardial fibrosis was evaluated after staining with Masson’s trichrome. (B) Histograms show the quantitative analysis of subendocardial fibrosis is shown as collagen area <i>vs.</i> total tissue area (100%, mean ± SEM; n = 4 animals per condition). (C) Histograms show type I and III collagen mRNA levels in cardiac tissue from iE and Veh. treated mice. (D) TGF-β signaling was activated in hearts from iE-treated mice. <i>Left panel</i>, representative blots of TRβ1, TRβ2, P-Smad, Smad, PAI-1 and FGF-2 of vehicle and iE treated mouse hearts (150 µg for 2 weeks). <i>Right panel,</i> shows the corresponding histograms representing the mean values <i>vs.</i> vehicle (100%, n = 4–6 animals). GAPDH was used to normalize all the target protein levels. *p<0.05, ***p<0.001 <i>vs.</i> vehicle.