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蛋白质组分析鉴定出与线粒体功能和炎症激活相关的蛋白质,这些蛋白质对脂肪性肝病的发病机制具有关键的调节作用。

Proteome analysis identified proteins associated with mitochondrial function and inflammation activation crucially regulating the pathogenesis of fatty liver disease.

机构信息

Shandong Key Laboratory of Animal Bioengineering and Disease Prevention, College of Animal Science and Technology, Shandong Agricultural University, Taian, Shandong, 271018, People's Republic of China.

出版信息

BMC Genomics. 2021 Sep 4;22(1):640. doi: 10.1186/s12864-021-07950-2.

Abstract

BACKGROUND

Fatty liver disease prevalently occurs in commercial postpartum dairies, resulting in a worldwide high culling rate because of their subsequent limitations of production and reproduction performance.

RESULTS

Fatty liver-specific proteome and acetylome analysis revealed that energy metabolism suppression closely associated with mitochondrial dysfunction and inflammation activation were shown to be remarkable biological processes underlying the development of fatty liver disease, furthermore, acetylation modification of proteins could be one of the main means to modulate these processes. Twenty pivotal genetic factors/genes that differentially expressing and being acetylation modified in liver were identified and proposed to regulate the pathogenesis of fatty liver dairies. These proteins were confirmed to be differentially expressing in individual liver tissue, eight of which being validated via immunohistochemistry assay.

CONCLUSIONS

This study provided a comprehensive proteome and acetylome profile of fatty liver of dairy cows, and revealed potential important biological processes and essential regulators in the pathogenesis of fatty liver disease. Expectantly, understanding the molecular mechanisms of the pathogenesis of fatty liver disease in dairies, as an animal model of non-alcoholic fatty liver disease (NAFLD) in human beings, which is a clinico-pathologically defined process associated with metabolic syndrome, could inspire and facilitate the development of efficacious therapeutic drugs on NAFLD.

摘要

背景

脂肪肝疾病在商业性产后奶牛场普遍发生,由于其后续生产和繁殖性能的限制,导致全球淘汰率很高。

结果

脂肪肝特异性蛋白质组和乙酰化组分析表明,能量代谢抑制与线粒体功能障碍和炎症激活密切相关,这表明这是脂肪肝疾病发展的显著生物学过程,此外,蛋白质的乙酰化修饰可能是调节这些过程的主要手段之一。鉴定出 20 个关键的遗传因素/基因,它们在肝脏中差异表达和乙酰化修饰,并被提出用于调节脂肪肝奶牛的发病机制。这些蛋白质在个体肝组织中被证实存在差异表达,其中 8 种通过免疫组织化学检测得到验证。

结论

本研究提供了奶牛脂肪肝的全面蛋白质组和乙酰化组图谱,揭示了脂肪肝发病机制中的潜在重要生物学过程和关键调节因子。预计,了解脂肪肝疾病在奶牛(一种非酒精性脂肪性肝病(NAFLD)的动物模型)中的发病机制的分子机制,作为与代谢综合征相关的临床病理定义过程,可能会激发并促进治疗 NAFLD 的有效治疗药物的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bf7/8418032/0705efcab5cd/12864_2021_7950_Fig1_HTML.jpg

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