TGF-β1 prevents simulated ischemia/reperfusion-induced cardiac fibroblast apoptosis by activation of both canonical and non-canonical signaling pathways
Author
dc.contributor.author
Vivar, Raúl
Author
dc.contributor.author
Humeres, Claudio
Author
dc.contributor.author
Ayala, Pedro
Author
dc.contributor.author
Olmedo, Ivonne
Author
dc.contributor.author
Catalán, Mabel
Author
dc.contributor.author
García Nannig, Lorena
Author
dc.contributor.author
Lavandero González, Sergio
Author
dc.contributor.author
Díaz Araya, Guillermo
Admission date
dc.date.accessioned
2019-01-29T13:56:03Z
Available date
dc.date.available
2019-01-29T13:56:03Z
Publication date
dc.date.issued
2013
Cita de ítem
dc.identifier.citation
Biochimica et Biophysica Acta - Molecular Basis of Disease, Volumen 1832, Issue 6, 2013, Pages 754-762
Identifier
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09254439
Identifier
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1879260X
Identifier
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10.1016/j.bbadis.2013.02.004
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/160040
Abstract
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.
Biochimica et Biophysica Acta - Molecular Basis of Disease
Keywords
dc.subject
Cardiac fibroblast
Keywords
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Cell death, apoptosis, ischemia/reperfusion
Keywords
dc.subject
TGF-β1
Título
dc.title
TGF-β1 prevents simulated ischemia/reperfusion-induced cardiac fibroblast apoptosis by activation of both canonical and non-canonical signaling pathways