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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.

Su Z, Yin J, Wang T, Sun Y, Ni P, Ma R, Zhu H, Zheng D, Shen H, Xu W, Xu H - J. Cell. Mol. Med. (2014)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China; Department of Immunology & Laboratory Immunology, Jiangsu University, Zhenjiang, China.

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HMGB1 blockade ameliorated cardiac fibrosis in EAM mice. After the model induction, the mice were killed on day 21 and day 54 respectively. The cardiac sections were stained with Sirius Red for collagen deposition and haematoxylin and eosin. (A) Haematoxylin and eosin-stained sections (20×). (B) Collagen was deposited in EAM mice heart accompanying the HMGB1 up-regulation (20×). (C) HMGB1 blockade decreased collagen deposition and ameliorated fibrosis (40×). A representative image is shown in the upper panel for each group. The fraction of positively stained areas is presented as mean ± SD with five mice for each group. *P < 0.05.
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fig03: HMGB1 blockade ameliorated cardiac fibrosis in EAM mice. After the model induction, the mice were killed on day 21 and day 54 respectively. The cardiac sections were stained with Sirius Red for collagen deposition and haematoxylin and eosin. (A) Haematoxylin and eosin-stained sections (20×). (B) Collagen was deposited in EAM mice heart accompanying the HMGB1 up-regulation (20×). (C) HMGB1 blockade decreased collagen deposition and ameliorated fibrosis (40×). A representative image is shown in the upper panel for each group. The fraction of positively stained areas is presented as mean ± SD with five mice for each group. *P < 0.05.

Mentions: In vivo, on day 21 after the model induction, the cardiomyocytes began swelling, lysis and eventually necrosis replacing by proliferated cardiac fibroblasts/myofibroblasts accompany HMGB1 up-regulation (Fig. 3A); this observation was further confirmed through collagen staining by sirius red. The percentage of sirius red-stained area significantly increased in EAM mice on day 54 [8 ± 6.5% (control) versus 86 ± 19% (day 54); Fig. 3B].


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.

Su Z, Yin J, Wang T, Sun Y, Ni P, Ma R, Zhu H, Zheng D, Shen H, Xu W, Xu H - J. Cell. Mol. Med. (2014)

HMGB1 blockade ameliorated cardiac fibrosis in EAM mice. After the model induction, the mice were killed on day 21 and day 54 respectively. The cardiac sections were stained with Sirius Red for collagen deposition and haematoxylin and eosin. (A) Haematoxylin and eosin-stained sections (20×). (B) Collagen was deposited in EAM mice heart accompanying the HMGB1 up-regulation (20×). (C) HMGB1 blockade decreased collagen deposition and ameliorated fibrosis (40×). A representative image is shown in the upper panel for each group. The fraction of positively stained areas is presented as mean ± SD with five mice for each group. *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196650&req=5

fig03: HMGB1 blockade ameliorated cardiac fibrosis in EAM mice. After the model induction, the mice were killed on day 21 and day 54 respectively. The cardiac sections were stained with Sirius Red for collagen deposition and haematoxylin and eosin. (A) Haematoxylin and eosin-stained sections (20×). (B) Collagen was deposited in EAM mice heart accompanying the HMGB1 up-regulation (20×). (C) HMGB1 blockade decreased collagen deposition and ameliorated fibrosis (40×). A representative image is shown in the upper panel for each group. The fraction of positively stained areas is presented as mean ± SD with five mice for each group. *P < 0.05.
Mentions: In vivo, on day 21 after the model induction, the cardiomyocytes began swelling, lysis and eventually necrosis replacing by proliferated cardiac fibroblasts/myofibroblasts accompany HMGB1 up-regulation (Fig. 3A); this observation was further confirmed through collagen staining by sirius red. The percentage of sirius red-stained area significantly increased in EAM mice on day 54 [8 ± 6.5% (control) versus 86 ± 19% (day 54); Fig. 3B].

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China; Department of Immunology & Laboratory Immunology, Jiangsu University, Zhenjiang, China.

Show MeSH
Related in: MedlinePlus