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The proliferation of cardiac fibroblasts (CFs) and excessive deposition of extracellular matrix are the predominant pathological characteristics of cardiac fibrosis. As the largest member of the nucleotide‑binding domain and leucine‑rich repeat (NLR) family, NLRC5 has been shown to be pivotal in the development of hepatic fibrosis. However, whether NLRC5 is involved in the pathogenesis of cardiac fibrosis remains to be elucidated. The present study aimed to investigate the role of NLRC5 and its mechanisms in regulating cardiac fibrosis. CFs were stimulated with transforming growth factor (TGF)‑β1 for various times and the mRNA and protein expression of NLRC5 was assessed using reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. In addition, CFs were transfected with small interfering (si)RNA targeting NLRC5 or scramble siRNA for 24 h and then stimulated with TGF‑β1 for 24 h. Subsequently, cell proliferation was measured using an MTT assay, whereas cell migration was evaluated using a Transwell migration assay. The protein expression levels of α‑smooth muscle actin, collagen I, connective tissue growth factor, phosphorylated‑Smad3 and Smad3 were measured using western blot analysis. The results demonstrated that NLRC5 was upregulated in TGF‑β1‑induced CFs. The knockdown of NLRC5 significantly inhibited cell proliferation and migration, and suppressed myofibroblast differentiation and the expression of pro‑fibrotic molecules in TGF‑β1‑treated CFs. Furthermore, the knockdown of NLRC5 attenuated TGF‑β1‑induced phosphorylation of small mothers against decapentaplegic (Smad)3 in the CFs. The results of the present study indicated that NLRC5 acted as a key regulator of pathological cardiac fibrosis, and NLRC5 silencing ameliorated cardiac fibrosis by inhibiting the TGF‑β1/Smad3 signaling pathway. These results suggested that NLRC5 may be a novel target for attenuating cardiac fibrosis.

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 µM) 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 α‑SMA, fibronectin, collagen I, TGF‑β1, 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‑β1 (TGF‑β1) and Smad3 phosphorylation in CFs. Taken together, these results suggest that diosgenin may inhibit Ang II‑induced ECM remodeling by suppressing the TGF‑β1/Smad3 signaling pathway in rat CFs. Therefore, diosgenin may possess therapeutic potential for the treatment of cardiac fibrosis.