Open AccessUp‐regulated HMGB 1 in EAM directly led to collagen deposition by a PKC β/Erk1/2‐dependent pathway: cardiac fibroblast/myofibroblast might be another source of HMGB 1
Author(s) -
Su Zhaoliang,
Yin Jingping,
Wang Ting,
Sun Yingkun,
Ni Ping,
Ma Rui,
Zhu Haitao,
Zheng Dong,
Shen Huiling,
Xu Wenlin,
Xu Huaxi
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12324
Subject(s) - myofibroblast , microbiology and biotechnology , fibroblast , chemistry , biology , biochemistry , medicine , fibrosis , pathology , in vitro
High mobility group box 1 ( HMGB 1), an important inflammatory mediator, is actively secreted by immune cells and some non‐immune cells or passively released by necrotic cells. HMGB 1 has been implicated in many inflammatory diseases. Our previous published data demonstrated that HMGB 1 was up‐regulated in heart tissue or serum in experimental autoimmune myocarditis ( EAM ); HMGB 1 blockade could ameliorate cardiac fibrosis at the last stage of EAM . And yet, until now, no data directly showed that HMGB 1 was associated with cardiac fibrosis. Therefore, the aims of the present work were to assess whether (1) up‐regulated HMGB 1 could directly lead to cardiac fibrosis in EAM ; (2) cardiac fibroblast/myofibroblasts could secrete HMGB 1 as another source of high‐level HMGB 1 in EAM ; and (3) HMGB 1 blockade could effectively prevent cardiac fibrosis at the last stage of EAM . Our results clearly demonstrated that HMGB 1 could directly lead to cardiac collagen deposition, which was associated with PKC β/Erk1/2 signalling pathway; furthermore, cardiac fibroblast/myofibroblasts could actively secrete HMGB 1 under external stress; and HMGB 1 secreted by cardiac fibroblasts/myofibroblasts led to cardiac fibrosis via PKC β activation by autocrine means; HMGB 1 blockade could efficiently ameliorate cardiac fibrosis in EAM mice.