Brd4 inhibition attenuates unilateral ureteral obstruction-induced fibrosis by blocking TGF-β-mediated Nox4 expression

• Published in: Redox biology Vol. 11; pp. 390 - 402
• Main Authors: Zhou, Baoshang, Mu, Jiao, Gong, Yi, Lu, Caibao, Zhao, Youguang, He, Ting, Qin, Zhexue
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2017; Elsevier
• Subjects: Actins - genetics; Actins - metabolism; Animals; Antioxidants - pharmacology; Azepines - pharmacology; Brd4; Cell Cycle Proteins; Cell Line, Transformed; Collagen Type IV - genetics; Collagen Type IV - metabolism; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Fibronectins - genetics; Fibronectins - metabolism; Fibrosis - etiology; Fibrosis - genetics; Fibrosis - pathology; Fibrosis - prevention & control; Humans; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Male; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; NADPH Oxidase 4 - genetics; NADPH Oxidase 4 - metabolism; Nox4; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; Renal fibrosis; Research Paper; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Smad3 Protein - genetics; Smad3 Protein - metabolism; TGF-β1; Transcription Factors - antagonists & inhibitors; Transcription Factors - genetics; Transcription Factors - metabolism; Transforming Growth Factor beta1 - antagonists & inhibitors; Transforming Growth Factor beta1 - pharmacology; Triazoles - pharmacology; Ureteral Obstruction - complications; Ureteral Obstruction - metabolism; Ureteral Obstruction - pathology; Ureteral Obstruction - surgery; Nox4; TGF-β1; Renal fibrosis; Brd4

Uncovering new therapeutic targets for renal fibrosis holds promise for the treatment of chronic kidney diseases. Bromodomain and extra-terminal (BET) protein inhibitors have been shown to effectively ameliorate pathological fibrotic responses. However, the pharmacological effects and underlying mec...