Diosgenin inhibits angiotensin II-induced extracellular matrix remodeling in cardiac fibroblasts through regulating the TGF-β1/Smad3 signaling pathway

The proliferation of cardiac fibroblasts (CFs) and deposition of extracellular matrix (ECM) proteins are pivotal in the development of cardiac fibrosis. Recent studies have indicated that diosgenin may inhibit high glucose-induced renal tubular fibrosis; however, to the best of our knowledge, no studies have focused on the effects of diosgenin on cardiac fibrosis. Therefore, the present study aimed to explore the effects of diosgenin on angiotensin II (Ang II)-induced ECM remodeling, and its possible mechanism in rat CFs. CFs were pre-incubated with diosgenin (1, 5 and 10 mu M) for 24 h and were then stimulated with Ang II (100 nM) for 24 h. Cell proliferation was estimated using the MTS assay. The expression levels of alpha-SMA, fibronectin, collagen I, TGF-beta 1, in addition to phosphorylation of Smad3 were detected by western blotting. The results demonstrated that diosgenin inhibited Ang II-induced CF proliferation and the differentiation of CFs to myofibroblasts. In addition, diosgenin was able to inhibit Ang II-induced ECM expression in rat CFs. Furthermore, diosgenin inhibited Ang II-induced expression of transforming growth factor-beta 1 (TGF-beta 1) and Smad3 phosphorylation in CFs. Taken together, these results suggest that diosgenin may inhibit Ang II-induced ECM remodeling by suppressing the TGF-beta 1/Smad3 signaling pathway in rat CFs. Therefore, diosgenin may possess therapeutic potential for the treatment of cardiac fibrosis.