Abstract
HLJ1 (also called DNAJB4) is a member of the DNAJ/Hsp40 family and plays an important role in regulating protein folding and activity. However, there is little information about the role of HLJ1 in the regulation of physiological function. In this study, we investigated the role of HLJ1 in blood coagulation using wild-type C57BL/6 mice and HLJ1-null (HLJ1-/-) mice. Western blot analysis and immunohistochemistry were used to assess the expression and distribution of HLJ1 protein, respectively. The tail bleeding assay was applied to assess the bleeding time and blood loss. A coagulation test was used for measuring the activity of extrinsic, intrinsic and common coagulation pathways. Thromboelastography was used to measure the coagulation parameters in the progression of blood clot formation. The results showed that HLJ1 was detectable in plasma and bone marrow. The distribution of HLJ1 was co-localized with CD41, the marker of platelets and megakaryocytes. However, genetic deletion of HLJ1 did not alter blood loss and the activity of extrinsic and intrinsic coagulation pathways, as well as blood clot formation, compared to wild-type mice. Collectively, these findings suggest that, although HLJ1 appears in megakaryocytes and platelets, it may not play a role in the function of blood coagulation under normal physiological conditions.
Highlights
Accepted: 11 February 2022Blood coagulation is a very delicate process including a series of rigorously controlled cellular and molecular events that produces a stable blood clot [1]
We isolated platelets from plasma and found that no soluble form of HLJ1 was detected in platelet-poor plasma; in contrast, the protein expression of HLJ1 in plasma was mainly restricted in platelets, as evidenced by the expression of HLJ1 being co-localized with CD41, the marker for platelets and megakaryocytes (Figure 1B,C,E)
We found that the protein expression of HLJ1 in bone marrow mainly appeared in megakaryocytes and platelets, as evidenced by the expression of HLJ1 being co-localized with CD41 in the bone marrow of WT mice (Figure 1D,F)
Summary
Accepted: 11 February 2022Blood coagulation is a very delicate process including a series of rigorously controlled cellular and molecular events that produces a stable blood clot [1]. Coagulation begins almost immediately after the vascular endothelial injury. Platelets immediately form a plug at the injury site, and blood coagulation factors other than factor VII simultaneously respond in a cascade to form fibrin strands to strengthen the platelet plug and thereby prevent the loss of blood [2,3,4]. It has been documented that coagulation pathways can be divided into “intrinsic” and “extrinsic” routes initiated by factor XII (FXII) and FVIIa/tissue factor (TF), respectively. These two routes are integrated into the downstream “common” pathway at the FXa/FVa (prothrombinase) complex [5]. The aggregated amyloid β peptide (Aβ) activates FXII in vitro, and the level of activated FXII is elevated in patients with Alzheimer’s disease (AD) and causes coagulation dysfunction [7]
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