PDF(Pubmed)
Abstract：
UNASSIGNED: Acetaminophen (APAP)-induced acute liver injury (ALI) is a global health issue characterised by an incomplete understanding of its pathogenesis and unsatisfactory therapies. NEK7 plays critical roles in both cell cycle regulation and inflammation. In the present study, we investigated the role and mechanism of NEK7 in APAP-induced ALI.
UNASSIGNED: In mice with NEK7 overexpression (hydrodynamic tail vein injection of NEK7 plasmids), hepatocyte-specific NEK7 knockout (cKO), and inducible NEK7 knockout (iKO), an overdose of APAP was administered to induce ALI. Liver injury was determined by an analysis of serum liver enzymes, pathological changes, inflammatory cytokines, and metabonomic profiles. In vitro, hepatocyte damage was evaluated by an analysis of cell viability, the reactive oxygen species levels, and mitochondrial function in different cell lines. Hepatocyte proliferation and the cell cycle status were determined by Ki-67 staining, EdU staining, and the cyclin levels.
UNASSIGNED: NEK7 was markedly downregulated in APAP-induced injured liver and damaged hepatocytes. NEK7 overexpression in the liver significantly alleviated APAP-induced liver injury, as shown by the restored liver function, reduced pathological injury, and decreased inflammation and oxidative stress, which was confirmed in a hepatocyte cell line. Moreover, both NEK7 cKO and iKO mice exhibited exacerbation of APAP-induced ALI. Finally, we determined that cyclin B1-mediated cell cycle progression could mediate the protective effect of NEK7 against APAP-induced ALI.
UNASSIGNED: Reduced NEK7 contributes to APAP-induced ALI, possibly by dysregulating cyclins and disturbing cell cycle progression.
UNASSIGNED: Acetaminophen-induced acute liver injury is one of the major global health issues, owing to its high incidence, potential severity, and limited therapeutic options. Our current understanding of its pathogenesis is incomplete. Herein, we have shown that reduced NEK7 (a protein with a key role in the cell cycle) exacerbates acetaminophen-induced acute liver injury. Hence, NEK7 could be a possible therapeutic target for the prevention or treatment of this condition.
UNASSIGNED: In mice with NEK7 overexpression (hydrodynamic tail vein injection of NEK7 plasmids), hepatocyte-specific NEK7 knockout (cKO), and inducible NEK7 knockout (iKO), an overdose of APAP was administered to induce ALI. Liver injury was determined by an analysis of serum liver enzymes, pathological changes, inflammatory cytokines, and metabonomic profiles. In vitro, hepatocyte damage was evaluated by an analysis of cell viability, the reactive oxygen species levels, and mitochondrial function in different cell lines. Hepatocyte proliferation and the cell cycle status were determined by Ki-67 staining, EdU staining, and the cyclin levels.
UNASSIGNED: NEK7 was markedly downregulated in APAP-induced injured liver and damaged hepatocytes. NEK7 overexpression in the liver significantly alleviated APAP-induced liver injury, as shown by the restored liver function, reduced pathological injury, and decreased inflammation and oxidative stress, which was confirmed in a hepatocyte cell line. Moreover, both NEK7 cKO and iKO mice exhibited exacerbation of APAP-induced ALI. Finally, we determined that cyclin B1-mediated cell cycle progression could mediate the protective effect of NEK7 against APAP-induced ALI.
UNASSIGNED: Reduced NEK7 contributes to APAP-induced ALI, possibly by dysregulating cyclins and disturbing cell cycle progression.
UNASSIGNED: Acetaminophen-induced acute liver injury is one of the major global health issues, owing to its high incidence, potential severity, and limited therapeutic options. Our current understanding of its pathogenesis is incomplete. Herein, we have shown that reduced NEK7 (a protein with a key role in the cell cycle) exacerbates acetaminophen-induced acute liver injury. Hence, NEK7 could be a possible therapeutic target for the prevention or treatment of this condition.
摘要：
未经证实：对乙酰氨基酚（APAP）诱导的急性肝损伤（ALI）是一个全球性的健康问题，其特征是对其发病机制的不完全了解和治疗方法不令人满意。NEK7在细胞周期调控和炎症中起关键作用。在本研究中,我们研究了NEK7在APAP诱导的ALI中的作用和机制。
UNASSIGNED：在NEK7过表达的小鼠中（流体动力学尾静脉注射NEK7质粒），肝细胞特异性NEK7敲除（cKO），和诱导型NEK7敲除（iKO），过量服用APAP诱导ALI.通过分析血清肝酶来确定肝损伤，病理变化,炎性细胞因子，和代谢学概况。体外，肝细胞损伤通过细胞活力分析进行评估，活性氧的水平，和线粒体在不同细胞系中的功能。通过Ki-67染色确定肝细胞增殖和细胞周期状态，EdU染色,和细胞周期蛋白水平。
未经证实：NEK7在APAP诱导的受损肝脏和受损肝细胞中显著下调。肝脏中NEK7的过表达显著减轻APAP诱导的肝损伤，如肝功能恢复所示，减少病理损伤，减少炎症和氧化应激，这在肝细胞细胞系中得到证实。此外，NEK7cKO和iKO小鼠均表现出APAP诱导的ALI加重。最后,我们确定细胞周期蛋白B1介导的细胞周期进程可以介导NEK7对APAP诱导的ALI的保护作用。
未经证实：降低的NEK7有助于APAP引起的ALI，可能是由于细胞周期蛋白失调和干扰细胞周期进程。
UASSIGNED：对乙酰氨基酚引起的急性肝损伤是全球主要健康问题之一，由于其发病率高，潜在的严重程度，和有限的治疗选择。我们目前对其发病机制的理解是不完整的。在这里，我们已经证明,NEK7(一种在细胞周期中起关键作用的蛋白质)减少会加剧对乙酰氨基酚诱导的急性肝损伤.因此，NEK7可能是预防或治疗这种疾病的可能的治疗靶标。
UNASSIGNED：在NEK7过表达的小鼠中（流体动力学尾静脉注射NEK7质粒），肝细胞特异性NEK7敲除（cKO），和诱导型NEK7敲除（iKO），过量服用APAP诱导ALI.通过分析血清肝酶来确定肝损伤，病理变化,炎性细胞因子，和代谢学概况。体外，肝细胞损伤通过细胞活力分析进行评估，活性氧的水平，和线粒体在不同细胞系中的功能。通过Ki-67染色确定肝细胞增殖和细胞周期状态，EdU染色,和细胞周期蛋白水平。
未经证实：NEK7在APAP诱导的受损肝脏和受损肝细胞中显著下调。肝脏中NEK7的过表达显著减轻APAP诱导的肝损伤，如肝功能恢复所示，减少病理损伤，减少炎症和氧化应激，这在肝细胞细胞系中得到证实。此外，NEK7cKO和iKO小鼠均表现出APAP诱导的ALI加重。最后,我们确定细胞周期蛋白B1介导的细胞周期进程可以介导NEK7对APAP诱导的ALI的保护作用。
未经证实：降低的NEK7有助于APAP引起的ALI，可能是由于细胞周期蛋白失调和干扰细胞周期进程。
UASSIGNED：对乙酰氨基酚引起的急性肝损伤是全球主要健康问题之一，由于其发病率高，潜在的严重程度，和有限的治疗选择。我们目前对其发病机制的理解是不完整的。在这里，我们已经证明,NEK7(一种在细胞周期中起关键作用的蛋白质)减少会加剧对乙酰氨基酚诱导的急性肝损伤.因此，NEK7可能是预防或治疗这种疾病的可能的治疗靶标。
