炎症因子在组织纤维化中介导组织型转谷氨酰胺酶的表达

Inflammatory cytokine mediated expression of tissue transglutaminase in tissue fibrosis

本研究在肝硬化病人的标本中,发现tTG和α-平滑肌肌动蛋白(alpha-smooth muscle actin,alpha-SMA)共位表达,表明tTG与肝星状细胞(hepatic stellate cells)的激活/转分化有关,与肝硬化的程度相关.烧伤病人的增生性瘢痕皮肤中tTG含量也相对于正常皮肤增加明显,并且分布于细胞外胶原蛋白之中,于alpha-SMA阳性细胞的周围.经体外星状细胞实验,白细胞介素1(interleukin 1,IL-1)能够诱导肝星状细胞在蛋白水平和mRNA水平表达tTG.同样,肿瘤坏死因子α(Tumor necrosis factor alpha,TNF-α)也能诱导表皮细胞(Hacat)表达tTG.表明,在组织损伤过程中,炎症反应可能引发细胞外基质的交联,促进纤维化.

The expression of tTG in human fibrotic tissues was assessed, and addressed how tTG is induced in fibrotic tissues. Through immunofluorescent staining we found that exclusive expression of tTG in fihrotic 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.