dc.creator | Vivar, Raúl | |
dc.creator | Humeres, Claudio | |
dc.creator | Ayala, Pedro | |
dc.creator | Olmedo, Ivonne | |
dc.creator | Catalán, Mabel | |
dc.creator | García Nannig, Lorena | |
dc.creator | Lavandero González, Sergio | |
dc.creator | Díaz Araya, Guillermo | |
dc.date.accessioned | 2019-01-29T13:56:03Z | |
dc.date.available | 2019-01-29T13:56:03Z | |
dc.date.created | 2019-01-29T13:56:03Z | |
dc.date.issued | 2013 | |
dc.identifier | Biochimica et Biophysica Acta - Molecular Basis of Disease, Volumen 1832, Issue 6, 2013, Pages 754-762 | |
dc.identifier | 09254439 | |
dc.identifier | 1879260X | |
dc.identifier | 10.1016/j.bbadis.2013.02.004 | |
dc.identifier | https://repositorio.uchile.cl/handle/2250/160040 | |
dc.description.abstract | Ischemia/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.language | en | |
dc.rights | http://creativecommons.org/licenses/by-nc-nd/3.0/cl/ | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Chile | |
dc.source | Biochimica et Biophysica Acta - Molecular Basis of Disease | |
dc.subject | Cardiac fibroblast | |
dc.subject | Cell death, apoptosis, ischemia/reperfusion | |
dc.subject | TGF-β1 | |
dc.title | TGF-β1 prevents simulated ischemia/reperfusion-induced cardiac fibroblast apoptosis by activation of both canonical and non-canonical signaling pathways | |
dc.type | Artículo de revista | |