title: Cytoplasmic translocation of HuR contributes to angiotensin II induced cardiac fibrosis.
abstract: Cardiac fibrosis is one of the key structural changes of the hypertrophied left ventricle in hypertensive heart disease. Increased angiotensin II was found to be important in the hypertension related fibrosis, while the underlying mechanism is unknown. In this study, we found that angiotensin II dose-dependently increased the expression of Col1a1, Col3a1 and α-smooth muscle actin, which were blocked by ROS (reactive oxygen species) scavenger N-acetyl cysteine (NAC). Mechanistically, angiotensin II induced robust ROS generation, which in turn induced cytoplasmic translocation of RNA binding protein HuR. Cytoplasmic translocated HuR increased TGFβ pathway activity and subsequent collagen synthesis. In contrast, knockdown of HuR nearly blocked angiotensin II induced TGFβ activation and collagen synthesis. Taken together, we here identified that angiotensin II promotes collagen synthesis in cardiac fibroblast through ROS-HuR-TGFβ pathway.
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, PR China; Department of Cardiology, 323 Hospital of PLA, Xi'an 710054, PR China.
authors.forename: Danna
authors.initials: D
authors.lastname: Bai
authors.affiliation: Department of Dermatology, Southwest Hospital, the Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ge
authors.affiliation: Department of Cardiology, 323 Hospital of PLA, Xi'an 710054, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Cardiology, 323 Hospital of PLA, Xi'an 710054, PR China; Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Xiaozhao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: wanghc@fmmu.edu.cn.
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: yanggd@fmmu.edu.cn.
authors.forename: Guodong
authors.initials: G
authors.lastname: Yang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D003593:Cytoplasm / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D051959:ELAV Proteins / Q000378:metabolism*; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D051959:ELAV Proteins; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D003094:Collagen; D000111:Acetylcysteine
keywords: Angiotensin II; Cardiac fibroblast; Collagen synthesis; HuR; TGFβ