Comparison of Thy–1 expression in human liver cirrhosis and different models of rat liver injury

Aims: Thy–1 is a glycophosphatidylinositol-linked outer membrane leaflet glycoprotein. Until now the precise biological role of Thy–1 remains still obscure.

One of the key characteristics of Thy–1 is that it´s expression often changes during cell differentiation. Changes in Thy–1 expression also accompany maturation and activation of several cell types, such as mesangial cells, mast cells, lung fibroblasts, thymocytes and astrocytes.

In the current study we investigated Thy–1 expression in human liver cirrhosis and different models of rat liver injury.

Methods: Thy–1 immunolocalization and mRNA expression was studied in human cirrhotic liver samples and in different models of rat liver injury (i.e. CCl₄-induced acute and chronic liver injury, 2-acetyl-aminofluorene/partial hepatectomy induced liver regeneration) compared to normal livers, as well as in isolated liver sinusoidal endothelial cells (SEC). Investigations at RNA level were performed by real time RT-PCR and Northern blot analysis, at protein level by indirect immunofluorescent single stainings on sequential sections or double stainings with anti-Thy–1, anti-Laminin, anti-Fibulin–2, smooth muscle alpha actin (SMA) and anti LYVE–1.

Results: In normal liver and in CCl₄ induced acute liver injury: Thy–1 positive cells were detected in the walls of the periportal vessels. Whereas in advanced stages of experimental fibrogenesis and in human cirrhotic liver samples it was detectable within the fibrotic tissue, throughout the full thickness of the massive scars infiltrating the liver parenchyma. During liver regeneration Thy–1 positive immunoreaction was found initially in the periportal area and expanded into the parenchymal sinusoids at later time points. Thy–1 positivity partially colocalized with Fibulin–2 and mRNA expression increased after CCl₄-induced liver damage.

Moreover, a part of Thy–1 positivity was detected in liver sinusoids, which could not be related to Fibulin–2 or SMA. Immunohistochemical colocalisation of Thy–1 with LYVE–1 and detection of Thy–1 at protein and mRNA level in SEC, displays Thy–1 expression in these cells as well. Conclusions: Our results provide evidence that Thy–1 identifies myofibroblasts and under some conditions SECs as well.

Key words

Thy-1 - liver cirrhosis - myofibroblast