Up‐regulated HMGB1 in EAM directly led to collagen deposition by a PKCβ/Erk1/2‐dependent pathway: cardiac fibroblast/myofibroblast might be another source of HMGB1

Journal of Cellular and Molecular Medicine

Zhaoliang Su²  Jingping Yin¹  Ting Wang²  Yingkun Sun²  Ping Ni²  Rui Ma¹  Haitao Zhu¹  Dong Zheng¹  Huiling Shen²  Wenlin Xu² 

[1] Department of Immunology & Laboratory Immunology, Jiangsu University, Zhenjiang, China;The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China

关键词: HMGB1;    experimental autoimmune myocarditis;    cardiac fibrosis;   

DOI  :  10.1111/jcmm.12324

来源: Wiley

【 摘 要 】

Abstract

High mobility group box 1 (HMGB1), an important inflammatory mediator, is actively secreted by immune cells and some non-immune cells or passively released by necrotic cells. HMGB1 has been implicated in many inflammatory diseases. Our previous published data demonstrated that HMGB1 was up-regulated in heart tissue or serum in experimental autoimmune myocarditis (EAM); HMGB1 blockade could ameliorate cardiac fibrosis at the last stage of EAM. And yet, until now, no data directly showed that HMGB1 was associated with cardiac fibrosis. Therefore, the aims of the present work were to assess whether (1) up-regulated HMGB1 could directly lead to cardiac fibrosis in EAM; (2) cardiac fibroblast/myofibroblasts could secrete HMGB1 as another source of high-level HMGB1 in EAM; and (3) HMGB1 blockade could effectively prevent cardiac fibrosis at the last stage of EAM. Our results clearly demonstrated that HMGB1 could directly lead to cardiac collagen deposition, which was associated with PKCβ/Erk1/2 signalling pathway; furthermore, cardiac fibroblast/myofibroblasts could actively secrete HMGB1 under external stress; and HMGB1 secreted by cardiac fibroblasts/myofibroblasts led to cardiac fibrosis via PKCβ activation by autocrine means; HMGB1 blockade could efficiently ameliorate cardiac fibrosis in EAM mice.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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