Factor XIII-A is involved in the regulation of gene expression in alternatively activated human macrophages.
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.
Töröcsik
Dániel
D
Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.
Szeles
Lajos
L
Paragh
György
G
Rakosy
Zsuzsa
Z
Bardos
Helga
H
Nagy
László
L
Balazs
Margit
M
Inbal
Aida
A
Adány
Róza
R
D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D003198:Computer Simulation; D005177:Factor XIII Deficiency / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D026122:Factor XIIIa / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D053263:Gene Regulatory Networks / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D046228:Microarray Analysis; D014945:Wound Healing / Q000235:genetics
D015847:Interleukin-4; D026122:Factor XIIIa