Zhaoliang Su, Jingping Yin and Ting Wang contributed equally.
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
Article first published online: 9 JUN 2014
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 18, Issue 9, pages 1740–1751, September 2014
How to Cite
Su, Z., Yin, J., Wang, T., Sun, Y., Ni, P., Ma, R., Zhu, H., Zheng, D., Shen, H., Xu, W. and Xu, H. (2014), 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, 18: 1740–1751. doi: 10.1111/jcmm.12324
- Issue published online: 10 SEP 2014
- Article first published online: 9 JUN 2014
- Manuscript Accepted: 14 APR 2014
- Manuscript Received: 1 OCT 2013
- National Natural Science Foundation of China. Grant Numbers: 81370084, 81001319, 81101677
- Postdoctoral Foundation of China. Grant Numbers: 2012M511705, 2013T60508
- Postdoctoral Foundation of Jiangsu Province. Grant Number: 1102129C
- Natural Science Foundation of Colleges and Universities in Jiangsu Province. Grant Number: 10KJB310003
- High-Tech of Jiangsu University. Grant Number: 11JDG128
- experimental autoimmune myocarditis;
- cardiac fibrosis
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.