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Diagn Pathol. 2015 Aug 6;10:134. doi: 10.1186/s13000-015-0348-3.

HMGB1: a novel protein that induced platelets active and aggregation via Toll-like receptor-4, NF-κB and cGMP dependent mechanisms.

Author information

1
Depatment of Haematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China. yaokkk223@163.com.
2
Laboratory of Emergency Medicine, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY, 11030, USA. Helyyl2243@163.com.
3
Department of Hemotology Xiangya Hospital, Central South University, Changsha, Hunan, 410078, PR China. Ganyyjj33@163.com.
4
Depatment of Haematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China. zeng223de@163.com.
5
Depatment of Haematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China. hope058@163.com.
6
Laboratory of Emergency Medicine, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY, 11030, USA. hope058@163.com.
7
Department of Hemotology Xiangya Hospital, Central South University, Changsha, Hunan, 410078, PR China. hope058@163.com.

Abstract

BACKGROUND:

Thrombotic diseases are a group of prevalent and life-threatening diseases. Selective inhibition of pathological thrombosis holds the key to treat variety of thrombotic diseases. The pathological thrombosis can be induced by either tissue necrosis and deregulated inflammation. HMGB1, as an important proinflammatory cytokine and a late mediator, also involves on thrombosis disease. However, the underlying mechanisms are not fully understood.

METHODS:

Immunofluorescence, ELISA assay, Platelet Aggregation, Thromboelastogram (TEG) analyzes. Flow cytometric analysis and Western blot analysis were used to investigated the role of HMGB1 in platelet aggregation and obtained following observations.

RESULTS:

By doing so, we obtained the following observations: i) Highly purified HMGB1 recombinant protein induces platelet aggregation and secretion in a dose-dependent manner in the presence of serum. ii) Low concentration of extracellular HMGB1 could synergistically promote subthreshold concentration of collagen or thrombin induced platelet aggregation. iii) Extracellular HMGB1 promoted platelet aggregation in a platelet-expressed GPIIb/IIIa-dependent manner. iv) We proposed that extracellular HMGB1 seems to promote the phosphorylation of GPIIb/IIIa and subsequent platelet aggregation via TLR4/NF-κB and cGMP pathway.

CONCLUSIONS:

In this study, we provide evidence for the hypothesis that HMGB1 interact with platelet might play an important role in the haemostasis and thrombotic diseases. Our research might be provide an interesting avenue for the treatment of thrombotic diseases in the future.

PMID:
26245198
PMCID:
PMC4527107
DOI:
10.1186/s13000-015-0348-3
[Indexed for MEDLINE]
Free PMC Article

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