title: 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.
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.
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yuan-Zheng
authors.initials: YZ
authors.lastname: Yang
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Fan
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D045304:Cytochromes c / Q000494:pharmacology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction; D051898:Smad1 Protein / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D051902:Smad5 Protein / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D051904:Smad8 Protein / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051902:Smad5 Protein; C497798:Smad5 protein, mouse; D051904:Smad8 Protein; C491621:Smad9 protein, mouse; D053773:Transforming Growth Factor beta1; D045304:Cytochromes c