1. Factor XIII-A is involved in the regulation of gene expression in alternatively activated human macrophages.
- Author
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Töröcsik D, Szeles L, Paragh G Jr, Rakosy Z, Bardos H, Nagy L, Balazs M, Inbal A, and Adány R
- Subjects
- Cell Differentiation, Cell Lineage, Cells, Cultured, Computer Simulation, Factor XIII Deficiency metabolism, Factor XIIIa genetics, Factor XIIIa immunology, Gene Expression Profiling, Gene Expression Regulation immunology, Gene Regulatory Networks immunology, Humans, Interleukin-4 immunology, Interleukin-4 metabolism, Macrophages immunology, Macrophages pathology, Microarray Analysis, Wound Healing genetics, Factor XIII Deficiency genetics, Factor XIII Deficiency immunology, Factor XIIIa metabolism, Macrophage Activation genetics, Macrophages metabolism
- Abstract
Factor XIII subunit A (FXIII-A) is one of the most overrepresented genes that is expressed during the alternative activation of macrophages. Based on its substrate profile and its cellular localisation, FXIII-A is thought to function as an intracellular/intranuclear transglutaminase. Our aim was to find role for the intracellular FXIII-A by comparing the microarray profiles of alternatively activated monocyte-derived macrophages. Microarray analyses of FXIII-A-deficient patients and healthy controls were evaluated, followed by functional clustering of the differentially expressed genes. After a 48-hour differentiation in the presence of interleukin 4 (IL4), 1,017 probes out of the 24,398 expressed in macrophages from FXIII-A- deficient samples were IL4 sensitive, while only 596 probes were IL4 sensitive in wild-type samples. Of these genes, 307 were induced in both the deficient and the wild-type macrophages. Our results revealed that FXIII-A has important role(s) in mediating gene expression changes in macrophages during alternative activation. Functional clustering of the target genes carried out using Cytoscape/BiNGO and Ingenuity Pathways Analysis programs showed that, in the absence of FXIII-A, the most prominent differences are related to immune functions and to wound response. Our findings suggest that functional impairment of macrophages at the level of gene expression regulation plays a role in the wound healing defects of FXIII-A-deficient patients.
- Published
- 2010
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