Exogenous cytochrome c inhibits the expression of transforming growth factor-β1 in a mouse model of sepsis-induced myocardial dysfunction via the SMAD1/5/8 signaling pathway.

The current study investigated the role of exogenous cytochrome c in sepsis-induced myocardial dysfunction (SIMD) using a mouse model and aimed to elucidate its effect on transforming growth factor-β1 (TGF-β1) expression during this process. A total of 75 male Kunming mice were randomly divided into the following five group: Normal (N, n=15); sham-operation (SHAM, n=15); sepsis (CLP, n=15); normal saline (NS, n=15); and cytochrome c (Cytc, n=15). Animals were sacrificed at 0, 6 or 12 h and the samples were analyzed using transmission electron microscopy, histopathological examination, reverse transcription-quantitative polymerase chain reaction, ELISA, protein analysis by western blotting. The SIMD model was developed and a significant downregulation of TGF-β1 gene expression, in addition to a reduction in the plasma and protein levels of TGF-β1 as well as the protein levels of TGF-β1-activated SMAD 1/5/8 were observed in the CLP group. The data from the current study indicate that using exogenous cytochrome c as a therapeutic strategy for SIMD is feasible, and may function via the downregulation of TGF-β1 expression through the SMAD 1/5/8 signaling pathway.