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探索多样化的凝血因子 XIII 亚单位表达数据集:一项生物信息学分析。

Exploring Diverse Coagulation Factor XIII Subunit Expression Datasets: A Bioinformatic Analysis.

机构信息

Institute of Experimental Hematology and Transfusion Medicine, University Hospital of Bonn, Building 043, Venusberg Campus 1, 53127 Bonn, Germany.

出版信息

Int J Mol Sci. 2022 Apr 25;23(9):4725. doi: 10.3390/ijms23094725.

Abstract

Coagulation factor XIII (FXIII) circulates in plasma as a pro-transglutaminase heterotetrameric complex (FXIIIAB), which upon activation by thrombin and calcium covalently crosslinks preformed fibrin polymers. The heterotetrameric complex is composed of a catalytic FXIIIA subunit and a protective/regulatory FXIII-B subunit coded by and genes, respectively. The catalytic FXIIIA subunit is encoded by the gene, expressed primarily in cells of mesenchymal origin, whereas the FXIIIB subunit encoded by the gene is expressed and secreted from hepatocytes. The plasma FXIIIA subunit, which earlier was believed to be secreted from cells of megakaryocytic lineage, is now understood to result primarily from resident macrophages. The regulation of the FXIII subunits at the genetic level is still poorly understood. The current study adopts a purely bioinformatic approach to analyze the temporal, time-specific expression array-data corresponding to both the subunits in specific cell lineages, with respect to the gene promoters. We analyze the differentially expressed genes correlated with and expression levels in an array of cell types, utilizing publicly available microarray data. We attempt to understand the regulatory mechanism underlying the variable expression of FXIIIA subunit in macrophages (M0, M1, M2 and aortic resident macrophages). Similarly, the FXIIIB subunit expression data from adult, fetal hepatocytes and embryonic stem cells derived hepatoblasts (hESC-hepatoblast) was analyzed. The results suggest regulatory dependence between the two FXIII subunits at the transcript level. Our analysis also predicts the involvement of the FXIIIA subunit in macrophage polarization, plaque stability, and inflammation.

摘要

凝血因子 XIII (FXIII) 在血浆中循环,作为一种前转谷氨酰胺酶异四聚体复合物 (FXIIIAB),其在凝血酶和钙离子的激活下,共价交联预先形成的纤维蛋白聚合物。该异四聚体复合物由催化 FXIIIA 亚基和保护/调节 FXIII-B 亚基组成,分别由 和 基因编码。催化 FXIIIA 亚基由 基因编码,主要在间充质来源的细胞中表达,而由 基因编码的 FXIIIB 亚基则由肝细胞表达和分泌。血浆 FXIIIA 亚基,以前被认为是由巨核细胞谱系的细胞分泌的,现在被认为主要来自驻留巨噬细胞。FXIII 亚基在基因水平上的调节仍知之甚少。本研究采用纯粹的生物信息学方法,分析特定细胞谱系中两个亚基的时间特异性表达数组数据,以及相应的基因启动子。我们分析了与 和 表达水平相关的差异表达基因在一系列细胞类型中的相关性,利用了公开的微阵列数据。我们试图理解在巨噬细胞 (M0、M1、M2 和主动脉驻留巨噬细胞) 中 FXIIIA 亚基可变表达的调节机制。同样,也分析了来自成人、胎儿肝细胞和胚胎干细胞衍生的肝母细胞 (hESC-hepatoblast) 的 FXIIIB 亚基表达数据。结果表明,在转录水平上两个 FXIII 亚基之间存在调节依赖性。我们的分析还预测了 FXIIIA 亚基在巨噬细胞极化、斑块稳定性和炎症中的参与。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab73/9099568/1cf574f2df2f/ijms-23-04725-g001.jpg

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