Estudio de la expresión de enzimas reparadoras del ADN implicadas en la ruta de señalizaciónmolecular dependiente de p53 (OGG1, SIRT1, FOXO1) en Lupus Eritematoso Sistémico (LES)

Abstract

[EN] Systemic lupus erythematosus (SLE) is characterized by defective apoptosis and autoantibody production against a nti - dsDNA and other nuclear and cytoplasmic components. The purpose of this study was to quantify mRNA and protein levels of Sirtuin1 (SIRT1) and its target proteins involved in DNA damage repair [8 - Oxoguanine glycosylase 1 ( OGG1), transcription factor p53 (p53) and forkhead box prot ein O1 (FOXO1)] in urinary sediment, and their association with lupus activity and renal histolog ical features. Briefly, urinary pellets from patients with SLE (n = 32) were analyzed for quantifying SIRT1, OGG1, FOXO1 and p53 expression by qRT - PCR. SIRT1 p rotein values were determined by immunoblot. Receiver operating characteristic curves (ROC) were calculated to investigate the discrimin ative power of the markers. The results showed a significant increase of S IRT1 mRNA and protein levels in patients with active LN (p < 0.01), and a decrease of OGG1, FOXO1 and p53 (p < 0.05 and p < 0.01, respectively). A si gnificant association was found between DNA repair molecules with anti - ds DNA, and SIRT1 with severity of histological features in LN (p < 0.05). Fina lly, 6 SIRT1 mRNA values were the most discr iminatory marker of LN (0.895, p < 0.0001 ). In conclusion, altered expression in DNA damage repair molecul es, SIRT1 and its targets OGG1, FOXO1 and p53 are associated to activity of disease, with the SIRT1 being a mark er of LN. The results lead to considering quantification of SIRT1 in urinary sediment as an attractive biomarker of renal active disease in SLE.

[ES] El Lupus Eritematoso Sistémico (LES) es una enfermedad autoinmune donde existe una alteración en el proceso de apoptosis, que hace que se acumulen fragmentos pequeños de ADN extracelular produciéndose autoanticuerpos frente a ellos (dsADN). La ruta de señalización de p53 es crucial en el proceso de apoptosis. Por ello, nos planteamos analizar si los niveles de expresión de enzimas y factores de transcripción implicados en esta ruta (SIRT1, OGG1 y FOXO1) estuviesen alterados en esta patología, y relacionados con el grado de activación