From Inflammation to the Onset of Fibrosis through A(2A) Receptors in Kidneys from Deceased Donors
Por:
Guillen-Gomez, E, Silva, I, Serra, N, Caballero, F, Leal, J, Breda, A, San Martin, R, Pastor-Anglada, M, Ballarin, JA, Guirado, L, Diaz-Encarnacion, MM
Publicada:
1 nov 2020
Resumen:
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.
Filiaciones:
Guillen-Gomez, E:
Fundacio Puigvert, Mol Biol Lab, Barcelona 08025, Spain
Fundacio Puigvert, Nephrol Dept, Barcelona 08025, Spain
Autonomous Univ Barcelona UAB, Fdn Renal Inigo Alvarez de Toledo FRIAT, REDinREN, Inst Invest Biosanitaria St Pau, Barcelona 08025, Spain
Silva, I:
Fundacio Puigvert, Nephrol Dept, Barcelona 08025, Spain
Autonomous Univ Barcelona UAB, Fdn Renal Inigo Alvarez de Toledo FRIAT, REDinREN, Inst Invest Biosanitaria St Pau, Barcelona 08025, Spain
Fundacio Puigvert, Renal Transplant Unit, Barcelona 08025, Spain
Serra, N:
Fundacio Puigvert, Nephrol Dept, Barcelona 08025, Spain
Autonomous Univ Barcelona UAB, Fdn Renal Inigo Alvarez de Toledo FRIAT, REDinREN, Inst Invest Biosanitaria St Pau, Barcelona 08025, Spain
Fundacio Puigvert, Renal Transplant Unit, Barcelona 08025, Spain
Caballero, F:
Univ Autonoma Barcelona, Dept Emergency Med & Transplant Coordinat, Hosp Santa Creu & St Pau, Barcelona 08041, Spain
Leal, J:
Univ Autonoma Barcelona, Dept Emergency Med & Transplant Coordinat, Hosp Santa Creu & St Pau, Barcelona 08041, Spain
Breda, A:
Autonomous Univ Barcelona UAB, Urol Dept, Fundacio Puigvert, Barcelona 08025, Spain
San Martin, R:
Univ Austral Chile, Fac Sci, Inst Biochem & Microbiol, Mol Pathol Lab, Valdivia 5110566, Chile
Pastor-Anglada, M:
Univ Barcelona, Inst Biomed IBUB, Natl Biomed Res Inst Liver & Gastrointestinal Dis, Dept Biochem & Mol Biomed, Barcelona 08028, Spain
Inst Recerca St Joan de Deu IR SJD, Esplugues De Llobregat B 08950, Spain
Ballarin, JA:
Fundacio Puigvert, Nephrol Dept, Barcelona 08025, Spain
Autonomous Univ Barcelona UAB, Fdn Renal Inigo Alvarez de Toledo FRIAT, REDinREN, Inst Invest Biosanitaria St Pau, Barcelona 08025, Spain
Guirado, L:
Fundacio Puigvert, Nephrol Dept, Barcelona 08025, Spain
Fundacio Puigvert, Renal Transplant Unit, Barcelona 08025, Spain
Diaz-Encarnacion, MM:
Fundacio Puigvert, Nephrol Dept, Barcelona 08025, Spain
Autonomous Univ Barcelona UAB, Fdn Renal Inigo Alvarez de Toledo FRIAT, REDinREN, Inst Invest Biosanitaria St Pau, Barcelona 08025, Spain
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