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Bmal1 Regulates Coagulation Factor Biosynthesis in Mouse Liver in Streptococcus oralis Infection
Lili Chen1,2, Shue Li1,2, Jiaming Nie1,2
1Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Streptococcus oralis (S. oralis) has been recognized as a fatal pathogen to cause multiorgan failure by contributing to the formation of microthrombus. Coagulation and fibrinolysis systems have been found under the control of circadian clock genes. This study aimed to explore the correlation between BMAL1 and coagulation factor biosynthesis in S. oralis infection. Mice were administered S. oralis to induce sepsis, and HepG2 cells were also infected by S. oralis. The expression of BMAL1 of hepatocytes was downregulated in the S. oralis infection group, leading to the downregulation of coagulation factor VII (FVII) and the upregulation of the coagulation factor XII (FXII) in vitro and in vivo. Furthermore, we confirmed that the deficiency of BAML1 contributed to the elevation of FVII and the decline in FXII by constructing BMAL1-deficiency (Bmal1-/-) mice. The current result showed that BMAL1 regulates FVII directly. Thus, a novel insight into the coagulation abnormality in S. oralis infection was gained that may optimize the treatment of sepsis by rescuing the expression of BMAL1 in the liver.
Insights
Streptococcus oralis infection disrupts the liver
Area of Science:
- * Circadian biology and chronobiology
- * Infectious diseases and pathology
- * Hematology and coagulation disorders
Background:
- * Streptococcus oralis (S. oralis) is a pathogen linked to multiorgan failure via microthrombus formation.
- * Circadian clock genes regulate coagulation and fibrinolysis systems.
- * The role of BMAL1 in S. oralis infection-induced coagulation abnormalities is not well understood.
Purpose of the Study:
- * To investigate the relationship between BMAL1 expression and coagulation factor biosynthesis during S. oralis infection.
- * To elucidate the regulatory role of BMAL1 in the context of sepsis caused by S. oralis.
Main Methods:
- * Induction of sepsis in mice using S. oralis administration.
- * Infection of HepG2 cells with S. oralis in vitro.
- * Analysis of BMAL1, coagulation factor VII (FVII), and coagulation factor XII (FXII) expression.
- * Utilizing BMAL1-deficient (Bmal1-/-) mice to assess the impact of BMAL1 deficiency.
Main Results:
- * S. oralis infection downregulated hepatocyte BMAL1 expression both in vivo and in vitro.
- * Downregulation of BMAL1 correlated with decreased FVII and increased FXII levels.
- * BMAL1 deficiency exacerbated FVII elevation and FXII decline.
- * Direct regulation of FVII by BMAL1 was confirmed.
Conclusions:
- * BMAL1 plays a critical role in regulating coagulation factor biosynthesis during S. oralis infection.
- * Disruption of BMAL1 contributes to coagulation abnormalities observed in sepsis.
- * Restoring BMAL1 expression in the liver may offer a novel therapeutic strategy for sepsis treatment.
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