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

Yang,Yuan‑Zheng; Fan,Ting‑Ting; Gao,Feng; Fu,Juan; Liu,Qiong

doi:10.3892/mmr.2015.3629

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

Authors:
- Yuan‑Zheng Yang
- Ting‑Ting Fan
- Feng Gao
- Juan Fu
- Qiong Liu
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Affiliations: Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: April 16, 2015 https://doi.org/10.3892/mmr.2015.3629
Pages: 2189-2196

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Abstract

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.

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