title: Cardiac Specific Overexpression of hHole Attenuates Isoproterenol-Induced Hypertrophic Remodeling through Inhibition of Extracellular Signal-Regulated Kinases (ERKs) Signalling.
abstract: The human Hole gene (hHole) encodes a six-transmembrane protein with 319- amino acids. Our previous study showed that hHole was strongly expressed in adult heart and may act as a suppressor of extracellular signal-regulated kinases (ERKs), overactivation of which contributed to pathological cardiac hypertrophy. In this study, it was observed that Hole expression was up-regulated in murine hypertrophic hearts. In a cardiac specific transgenic mouse model, it was observed that overexpression of hHole specifically in heart attenuated cardiac hypertrophy and fibrosis induced by isoproterenol (ISO), with blunted transcriptions of ERK1/2, total ERK1/2 proteins and phosphorylated ERK1/2 (p-ERK1/2) levels. Furthermore, overexpression of hHole in mice by hydrodynamic tail-vein injection with hHole plamids also inhibited cardiac hypertrophy induced by ISO. Our work identified hHole as a novel repressor of cardiac hypertrophy, and provided new insights into the possible target for the prevention or treatment of cardiac diseases.
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Yuan
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.forename: L
authors.initials: L
authors.lastname: Cao
authors.forename: Q
authors.initials: Q
authors.lastname: Zeng
authors.forename: Z
authors.initials: Z
authors.lastname: Jiang
authors.forename: X
authors.initials: X
authors.lastname: Ye
authors.forename: Y
authors.initials: Y
authors.lastname: Wan
authors.forename: X
authors.initials: X
authors.lastname: Peng
authors.forename: Y
authors.initials: Y
authors.lastname: Deng
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Dai
authors.forename: S
authors.initials: S
authors.lastname: Luo
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.forename: X
authors.initials: X
authors.lastname: Mo
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.affiliation: The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha 410081, China. liyongqing2002cn@aliyun.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000139:chemically induced / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007545:Isoproterenol / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D020257:Ventricular Remodeling / Q000187:drug effects / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C503401:TMEM121 protein, human; D007545:Isoproterenol