Inhibition of BRD4 Attenuates ER Stress-induced Renal Ischemic-Reperfusion Injury
Paula Díaz-Bulnes, Ramón María Alvargonzález Rodríguez, Elisenda Bañón-Maneus, María Laura Sáiz, Cristian Ruiz Bernet, Viviana Corte-Iglesias, María José Ramírez-Bajo, Marta Lazo-Rodríguez, Isaac Tamargo‐Gómez, Raúl R. Rodrigues-Díez, Ana B. Sanz, Carmen Díaz‐Corte, Marta Ruiz‐Ortega, Fritz Diekmann, Ana M. Aransay, Carlos López‐Larrea, Beatriz Suárez-Álvarez
Abstract
genes, low KIM-1 and NGAL levels and recovery of the serum creatinine and blood urea nitrogen levels. To determine the molecular pathways regulated by ATF4 and XBP1, we performed stable knockout of both transcription factors using CRISPR-Cas9 and RNA sequencing. The pathways triggered under ER stress were mainly XBP1-dependent, associated with an adaptive UPR, and partially regulated by JQ1. Meanwhile, treatment with JQ1 downmodulated most of the pathways regulated by ATF4 and related to the pathological processes during exacerbated UPR activation. Thus, BRD4 inhibition could be useful for curbing the maladaptive UPR activation mechanisms, thereby ameliorating the progression of renal disease.