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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/49441
Genetically Modified Macrophages and Renal Regeneration
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[spa] Después de la lesión isquémica en el riñón, los macrófagos activados alternativamente o M2 no solo participan en la reparación del daño sino son factores clave en la resolución de la inflamación. La obtención de este fenotipo particular es un proceso controlado por la desregulación de una serie de genes. Modulando estos genes, se podría controlar el fenotipo y las funciones de los macrófagos, con el objetivo de nuevos enfoques en el tratamiento de FRA. El primer objetivo de este estudio fue identificar los genes que están implicados en la reparación de tejidos y que están relacionados con los macrófagos M2. Por genómica funcional hemos identificado la expresión de 14 genes cruciales para la inducción de la capacidad regeneradora endógena del riñón y modulados por la presencia de macrófagos. A continuación hemos demostrado que la modulación del gen Ivns1abp puede modular la reparación renal. En concreto hemos demostrado que la sobre-expresión del gen Ivns1abp en macrófagos puede mejorar su capacidad regenerativa y cambiar su fenotipo hacia M2, provocando la modulación de su estado inflamatorio y aumento de su resistencia frente la inflamación. Se demostró además que el silenciamiento del gen Ivns1abp en macrófagos disminuye su capacidad reparadora y fagocítica transformando su fenotipo a M1. Como ultimo, hemos definido las vías que regulan la transcripción del gen Ivns1abp. Hemos demostrado que la expresión del gen Ivns1abp en los macrófagos está regulada por el factor del trascripción c-myc y modulada por la presencia de citoquinas, determinando el destino de la célula.
[eng] After ischemic damage in kidney, alternatively activated or M2 macrophages are key players in resolving inflammation and participating in kidney repair. Obtaining this particular phenotype is a process controlled by deregulation of a series of genes. Modulation of those genes could result in controlling macrophages phenotype and functions, aiming new approaches in resolving ARF. The first aim of this study was to identify genes that are related to M2 macrophages that are involved in tissue repair. By functional genomics we have identified the expression of 14 genes crucial for the induction of the endogenous reparative capacity of the kidney that are modulated by the presence of macrophages. We also demonstrated that modulation of Ivns1abp gene can modulate renal repair. More concrete we show that over-expression of the Ivns1abp gene can enhance macrophages regenerative capacity and switch their phenotype towards M2, provoking modulation of their inflammatory state and increasing its resistance against inflammation inputs. We also demonstrated that silencing of the Ivns1abp genet to macrophages leads them to acquire a M1 phenotype and decrease their reparative and phagocytosis capacity. As a last step, we define pathways that regulate the transcription of the Ivns1abp gene. We show that Ivns1abp gene expression in macrophages is regulated by the c-myc transcription factor and modulated by the presence of cytokines determining cell fate.
[eng] After ischemic damage in kidney, alternatively activated or M2 macrophages are key players in resolving inflammation and participating in kidney repair. Obtaining this particular phenotype is a process controlled by deregulation of a series of genes. Modulation of those genes could result in controlling macrophages phenotype and functions, aiming new approaches in resolving ARF. The first aim of this study was to identify genes that are related to M2 macrophages that are involved in tissue repair. By functional genomics we have identified the expression of 14 genes crucial for the induction of the endogenous reparative capacity of the kidney that are modulated by the presence of macrophages. We also demonstrated that modulation of Ivns1abp gene can modulate renal repair. More concrete we show that over-expression of the Ivns1abp gene can enhance macrophages regenerative capacity and switch their phenotype towards M2, provoking modulation of their inflammatory state and increasing its resistance against inflammation inputs. We also demonstrated that silencing of the Ivns1abp genet to macrophages leads them to acquire a M1 phenotype and decrease their reparative and phagocytosis capacity. As a last step, we define pathways that regulate the transcription of the Ivns1abp gene. We show that Ivns1abp gene expression in macrophages is regulated by the c-myc transcription factor and modulated by the presence of cytokines determining cell fate.
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MASTORA, Chrysoula. Genetically Modified Macrophages and Renal Regeneration. [consulta: 15 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/49441]