Factor XIII-A is involved in the regulation of gene expression in alternatively activated human macrophages

Dániel Töröcsik, Lajos Széles, György Paragh, Zsuzsa Rákosy, Helga Bárdos, László Nagy, Margit Balázs, Aida Inbal, Róza Ádány

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)709-717
Number of pages9
JournalThrombosis and Haemostasis
Volume104
Issue number4
DOIs
StatePublished - Oct 1 2010

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Keywords

  • Factor XIII-A
  • Interleukin 4
  • Macrophage
  • Wound healing

ASJC Scopus subject areas

  • Hematology

Cite this

Töröcsik, D., Széles, L., Paragh, G., Rákosy, Z., Bárdos, H., Nagy, L., Balázs, M., Inbal, A., & Ádány, R. (2010). Factor XIII-A is involved in the regulation of gene expression in alternatively activated human macrophages. Thrombosis and Haemostasis, 104(4), 709-717. https://doi.org/10.1160/TH09-11-0805