Abstract Number: PB0724
Meeting: ISTH 2020 Congress
Background: The plasma circulating pro-transglutaminase coagulation factor XIII is a heterotetrameric protein complex, composed of dimeric FXIII-A2 and FXIII-B2 subunits both of which are expressed in different cell types. While the FXIII- A2 subunit is expressed in a variety of cell types which include platelets, monocytes and macrophages, although recently it has been demonstrated that the major contributor to plasma FXIII-A2 are resident macrophages. The FXIII-B2 subunit on the other hand is exclusively expressed in hepatocytic cell lineage. Little is known of FXIII gene´s promoter regions in the context of their transcriptional regulation.
Aims: To investigate the transcriptomic profile of coagulation FXIII genes.
Methods: Our current study presents a bioinformatic analyses of publicly available selective microarray expression datasets from cells expressing FXIII subunits i.e. monocyte derived macrophages and hepatocytes/ hepatic-progenitor cells.
Results: The MXDI and HES2 transcription factors binding to the same EBOX binding site showed positive and negative significant correlation to FXIII-A2 expression respectively in monocyte derived macrophages. Similarly, HES6 binding to the EBOX binding site was observed to be negatively correlated with FXIII-B2 expression, whereas RFX5 was found to upregulate FXIII-B2 in hepatocytes and hepatic progenitor cells. Transcriptional levels of the two subunits also show an inverse correlation within time specific array data sets raising the possibility that the two subunits could regulate each other´s levels through indirect mechanisms. Gene ontology analysis of differentially expressed genes in time specific array data sets suggests the participation of the two FXIII subunits in newer (sterol biosynthesis) and also previously suggested (immune response/wound healing/membrane invagination) biological pathways outside or indirectly related to the coagulation pathway.
Conclusions: Our investigation reveals that both FXIII-A2 and FXIII-B2 subunits are regulated by common transcription factors. Enrichment of correlated genes with FXIII-subunits suggests pleiotropic roles.
To cite this abstract in AMA style:Jamil MA, Singh S, Wolberg AS, El-Maarri O, Oldenburg J, Biswas A. Transcriptome Profiling of Coagulation Factor XIII Genes: Implications for Pleiotropic Pathways and Inter-Subunit Regulation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/transcriptome-profiling-of-coagulation-factor-xiii-genes-implications-for-pleiotropic-pathways-and-inter-subunit-regulation/. Accessed October 1, 2023.
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