dc.creatorVivar, Raúl
dc.creatorHumeres, Claudio
dc.creatorAyala, Pedro
dc.creatorOlmedo, Ivonne
dc.creatorCatalán, Mabel
dc.creatorGarcía Nannig, Lorena
dc.creatorLavandero González, Sergio
dc.creatorDíaz Araya, Guillermo
dc.date.accessioned2019-01-29T13:56:03Z
dc.date.available2019-01-29T13:56:03Z
dc.date.created2019-01-29T13:56:03Z
dc.date.issued2013
dc.identifierBiochimica et Biophysica Acta - Molecular Basis of Disease, Volumen 1832, Issue 6, 2013, Pages 754-762
dc.identifier09254439
dc.identifier1879260X
dc.identifier10.1016/j.bbadis.2013.02.004
dc.identifierhttps://repositorio.uchile.cl/handle/2250/160040
dc.description.abstractIschemia/reperfusion injury is a major cause of myocardial death. In the heart, cardiac fibroblasts play a critical role in healing post myocardial infarction. TGF-β1 has shown cardioprotective effects in cardiac damage; however, if TGF-β1 can prevent cardiac fibroblast death triggered by ischemia/reperfusion is unknown. Therefore, we test this hypothesis, and whether the canonical and/or non-canonical TGF-β1 signaling pathways are involved in this protective effect. Cultured rat cardiac fibroblasts were subjected to simulated ischemia/reperfusion. Cell viability was analyzed by trypan blue exclusion and propidium iodide by flow cytometry. The processing of procaspases 8, 9 and 3 to their active forms was assessed by Western blot, whereas subG1 population was evaluated by flow cytometry. Levels of total and phosphorylated forms of ERK1/2, Akt and Smad2/3 were determined by Western blot. The role of these signaling pathways on the protective effect of TGF-β1 was studied using specific chemical inhibitors. Simulated ischemia over 8 h triggers a significant cardiac fibroblast death, which increased by reperfusion, with apoptosis actively involved. These effects were only prevented by the addition of TGF-β1 during reperfusion. TGF-β1 pretreatment increased the levels of phosphorylated forms of ERK1/2, Akt and Smad2/3. The inhibition of ERK1/2, Akt and Smad3 also blocked the preventive effects of TGF-β1 on cardiac fibroblast apoptosis induced by simulated ischemia/reperfusion. Overall, our data suggest that TGF-β1 prevents cardiac fibroblast apoptosis induced by simulated ischemia–reperfusion through the canonical (Smad3) and non canonical (ERK1/2 and Akt) signaling pathways.
dc.languageen
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
dc.sourceBiochimica et Biophysica Acta - Molecular Basis of Disease
dc.subjectCardiac fibroblast
dc.subjectCell death, apoptosis, ischemia/reperfusion
dc.subjectTGF-β1
dc.titleTGF-β1 prevents simulated ischemia/reperfusion-induced cardiac fibroblast apoptosis by activation of both canonical and non-canonical signaling pathways
dc.typeArtículo de revista


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