Inflammatory Cytokine Mediated Expression of Tissue Transglutaminase in Tissue Fibrosis

Abstract:

Tissue transglutaminase (tTG) is an enzyme (EC2.3.2.13) being able to crosslink polypeptides into iso-peptide bonds. Fibrosis is mediated by myofibroblasts, which produce extracellular matrix (ECM) and generate wound contraction. Here we assessed the expression of tGT in human fibrotic tissues, and addressed how tGT is induced in fibrotic tissues. Through immunofluorescent staining we found that exclusive expression of tTG in fibrotic septa of human cirrhotic liver, co-localized with the alpha-smooth muscle (alpha-SMA) positive cells, implying hepatic stellate cells for tTG expression. Absence from normal skin, tTG was highly expressed in the human hypertrophic scar, which was also intimately associated with the alpha-SMA positive cells. In vitro experiment showed that interleukin-1 could induce tTG expression by rat primary hepatic stellate cells (HSCs). Likewise, TNF-α could induce tTG expression by skin epithelial cells. Thus, our work indicates that inflammatory cytokines may play a critical role in induction of tTG in fibrosis formation.