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

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.

PMID: 35563115