Toll-Like Receptor 4 Activation Prevents Rat Cardiac Fibroblast Death Induced by Simulated Ischemia/Reperfusion

Simple item page
dc.contributor.authorParra-Flores, Pablo
dc.contributor.authorEspitia-Corredor, Jenaro
dc.contributor.authorEspinoza-Perez, Claudio
dc.contributor.authorQueirolo, Cristian
dc.contributor.authorAyala, Pedro
dc.contributor.authorBruggendieck, Francisca
dc.contributor.authorSalas-Hernandez, Aimee
dc.contributor.authorPardo-Jimenez, Viviana
dc.contributor.authorDiaz-Araya, Guillermo
dc.date.accessioned2025-01-20T22:17:59Z
dc.date.available2025-01-20T22:17:59Z
dc.date.issued2021
dc.description.abstractDeath of cardiac fibroblasts (CFs) by ischemia/reperfusion (I/R) has major implications for cardiac wound healing. In in vivo models of myocardial infarction, toll-like receptor 4 (TLR4) activation has been reported as a cardioprotector; however, it remains unknown whether TLR4 activation can prevent CF death triggered by simulated I/R (sI/R). In this study, we analyzed TLR4 activation in neonate CFs exposed to an in vitro model of sI/R and explored the participation of the pro-survival kinases Akt and ERK1/2. Simulated ischemia was performed in a free oxygen chamber in an ischemic medium, whereas reperfusion was carried out in normal culture conditions. Cell viability was analyzed by trypan blue exclusion and the MTT assay. Necrotic and apoptotic cell populations were evaluated by flow cytometry. Protein levels of phosphorylated forms of Akt and ERK1/2 were analyzed by Western blot. We showed that sI/R triggers CF death by necrosis and apoptosis. In CFs exposed only to simulated ischemia or only to sI/R, blockade of the TLR4 with TAK-242 further reduced cell viability and the activation of Akt and ERK1/2. Preconditioning with lipopolysaccharide (LPS) or treatment with LPS in ischemia or reperfusion was not protective. However, LPS incubation during both ischemia and reperfusion periods prevented CF viability loss induced by sI/R. Furthermore, LPS treatment reduced the sub-G1 population, but not necrosis of CFs exposed to sI/R. On the other hand, the protective effects exhibited by LPS were abolished when TLR4 was blocked and Akt and ERK1/2 were inhibited. In conclusion, our results suggest that TLR4 activation protects CFs from apoptosis induced by sI/R through the activation of Akt and ERK1/2 signaling pathways.
dc.description.funderFondo Nacional de Desarrollo Cientifico y Tecnologico, FONDECYT, Chile
dc.fuente.origenWOS
dc.identifier.doi10.3389/fcvm.2021.660197
dc.identifier.issn2297-055X
dc.identifier.urihttps://doi.org/10.3389/fcvm.2021.660197
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94564
dc.identifier.wosidWOS:000663922700001
dc.language.isoen
dc.revistaFrontiers in cardiovascular medicine
dc.rightsacceso restringido
dc.subjectcardiac fibroblasts
dc.subjectischemia/reperfusion
dc.subjectTLR4
dc.subjectLPS
dc.subjectapoptosis
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleToll-Like Receptor 4 Activation Prevents Rat Cardiac Fibroblast Death Induced by Simulated Ischemia/Reperfusion
dc.typeartículo
dc.volumen8
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas