PB0715 - Exploring diverse coagulation Factor XIII subunit expression datasets: A bioinformatic analysis

Background: Coagulation Factor XIII (FXIII) circulates in plasma as a pro-transglutaminase complex composed of the catalytic FXIIIA and carrier/regulatory FXIIIB subunits. It functions by crosslinking fibrin clot making it resistant to premature fibrinolysis. The FXIIIA subunit in plasma is expressed from resident macrophages, while the FXIIIB subunit is contributed by hepatocytes. Very little is known on the intracellular regulation of these two subunits.

Aims: The current study uses a purely bioinformatics approach to understand the intracellular regulatory mechanism underlying both FXIIIA and FXIIIB subunits.

Methods: Expression data were extracted from NCBI GEO (GSE128303, GSE98324, GSE39157, and GSE41571) for macrophages (time-series), hepatic progenitor, hepatocytes and human embryonic stem cells derived hepatoblasts. Data were background corrected, normalized, and filtered based on the array platform using R. Bioinformatics tools (Qlucore Omics Explorer, TRANSFAC, and Cytoscape) were used for identifying transcriptional regulation of the differentially expressed genes between cell types and generating networks for visualization. Ingenuity pathway analysis (IPA) was used to identify upstream regulators of differentially expressed genes (Fig. 1).

Results: Genes correlated with F13A1 and F13B genes are linked to several biological processes including immune response. Both FXIII subunits show similarity in transcription factor binding suggesting the possibility of inter-regulation (e.g. HES2, MXD1, HES6). On profiling the array data from M1 and M2 macrophages a strong expression of F13A1 in M2 was observed, the time-based array indicates that FXIII-A most likely contributes towards macrophage polarization. No differential expression of F13A1 in resident macrophages derived from ruptured vs vulnerable plaques was observed, indicating that its constitutive expression of F13A1 is not responsible for plaque initiation/progression, but maintenance.

Conclusion(s): Bioinformatic expression profiling reveals that both FXIIIA and FXIIIB subunit have roles beyond coagulation, most likely in immune response. Sharing of transcription factor binding elements suggests the possiblity of interregulation between the FXIIIA and FXIIIB subunits.