DIM attenuates TGF-β1-induced myofibroblast differentiation in neonatal rat cardiac fibroblasts.

3,3'-Diindolylmethane (DIM) is a natural component of cruciferous plants. Previous studies have shown that DIM has multiple physiological effects including anti-angiogenic, anti-inflammatory and anti-cancer effect. However, little is known about the role of DIM on myofibroblast differentiation and extracellular matrix (ECM) production. This study investigated the effect of DIM on myofibroblast differentiation and ECM production in neonatal rat cardiac fibroblasts induced by transforming growth factor β1 (TGF-β1). We found that DIM blunted TGF-β1 induced conversion of cardiac fibroblast into myofibroblast, and reduced the mRNA and protein expressions of α-smooth muscle actin (α-SMA). Furthermore, DIM also significantly decreased the mRNA expression of fibrosis markers (Collagen I, Collagen III, connective tissue growth factor (CTGF) in neonatal rat cardiac fibroblasts induced by TGF-β1. DIM attenuated the phosphorylation AKT and glycogen synthase kinase-3β (GSK-3β) induced by TGF-β1. Our results showed that DIM was a potential drug to attenuate myofibroblast differentiation and excessive ECM production induced by TGF-β1 through down-regulated AKT/GSK-3β signaling pathways.