title: Disruption of tumor necrosis factor receptor associated factor 5 exacerbates pressure overload cardiac hypertrophy and fibrosis.
abstract: The cytoplasmic signaling protein tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5), which was identified as a signal transducer for members of the TNF receptor super-family, has been implicated in several biological functions in T/B lymphocytes and the innate immune response against viral infection. However, the role of TRAF5 in cardiac hypertrophy has not been reported. In the present study, we investigated the effect of TRAF5 on the development of pathological cardiac hypertrophy induced by transthoracic aorta constriction (TAC) and further explored the underlying molecular mechanisms. Cardiac hypertrophy and function were evaluated with echocardiography, hemodynamic measurements, pathological and molecular analyses. For the first time, we found that TRAF5 deficiency substantially aggravated cardiac hypertrophy, cardiac dysfunction and fibrosis in response to pressure overload after 4 weeks of TAC compared to wild-type (WT) mice. Moreover, the mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway was more activated in TRAF5-deficient mice than WT mice. In conclusion, our results suggest that as an intrinsic cardioprotective factor, TRAF5 plays a crucial role in the development of cardiac hypertrophy through the negative regulation of the MEK-ERK1/2 pathway. J. Cell. Biochem. 115: 349-358, 2014. © 2013 Wiley Periodicals, Inc.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, PR China.
authors.forename: Zhouyan
authors.initials: Z
authors.lastname: Bian
authors.forename: Jia
authors.initials: J
authors.lastname: Dai
authors.forename: Nakano
authors.initials: N
authors.lastname: Hiroyasu
authors.forename: Hongjing
authors.initials: H
authors.lastname: Guan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Lihua
authors.initials: L
authors.lastname: Gan
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Zong
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fangfang
authors.initials: F
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.forename: Difei
authors.initials: D
authors.lastname: Shen
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.forename: Qizhu
authors.initials: Q
authors.lastname: Tang
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003250:Constriction; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D005355:Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D048015:TNF Receptor-Associated Factor 5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D048015:TNF Receptor-Associated Factor 5; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: CARDIAC HYPERTROPHY; FIBROSIS; TRAF5