From Inflammation to the Onset of Fibrosis through A(2A) Receptors in Kidneys from Deceased Donors
Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (A(2A)R) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p11751 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11751 |
| Access Level: | acceso abierto |
| Palabra clave: | fibrosis macrophage inflammation transplant kidney purinome adenosine receptor |
| Sumario: | Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (A(2A)R) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47 DD and 21 living donors (LD)) were used to analyze expression levels and activated intracellular pathways related to inflammatory and pro-fibrotic processes. A(2A)R expression and PKA pathway were enhanced in DD kidneys. A(2A)R gene expression correlated with TGF-beta 1 and other profibrotic markers, as well as CD163, C/EBP beta, and Col1A1, which are highly expressed in DD kidneys. TNF-alpha mRNA levels correlated with profibrotic and anti-inflammatory factors such as TGF-beta 1 and A(2A)R. Experiments with THP-1 cells point to the involvement of the TNF-alpha/NF-kappa B pathway in the up-regulation of A(2A)R, which induces the M2 phenotype increasing CD163 and TGF-beta 1 expression. In DD kidneys, the TNF-alpha/NF-kappa B pathway could be involved in the increase of A(2A)R expression, which would activate the PKA-CREB axis, inducing the macrophage M2 phenotype, TGF-beta 1 production, and ultimately, fibrosis. Thus, in inflamed DD kidneys, an increase in A(2A)R expression is associated with the onset of fibrosis, which may contribute to graft dysfunction and prognostic differences between DD and LD transplants. |
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