Paula Diaz-Bulnes, Ramon M Rodríguez, Elisenda Banon-Maneus, María Laura Saiz, Cristian Ruiz Bernet, Viviana Corte-Iglesias, Maria Jose Ramirez-Bajo, Marta Lazo-Rodriguez, Isaac Tamargo-Gómez, Raúl R Rodrigues-Diez, Ana B Sanz, Carmen Diaz-Corte, Marta Ruiz-Ortega, Fritz Diekmann, Ana M Aransay, Carlos Lopez-Larrea, Beatriz Suarez-Alvarez
Renal ischemia-reperfusion injury (IRI) leads to endoplasmic reticulum (ER) stress, thereby initiating the unfolded protein response (UPR). When sustained, this response may trigger the inflammation and tubular cell death that acts to aggravate the damage. Here, we show that knockdown of the BET epigenetic reader BRD4 reduces the expression of ATF4 and XBP1 transcription factors under ER stress activation. BRD4 is recruited to the promoter of these highly acetylated genes, initiating gene transcription. Administration of the BET protein inhibitor, JQ1, one hour after renal damage induced by bilateral IRI, reveals reduced expression of ATF4 and XBP1 genes, low KIM-1 and NGAL levels and recovery of the serum creatinine and blood urea nitrogen levels...
2024: International Journal of Biological Sciences