Smoothelin, a new marker to determine the origin of liver fibrogenic cells

Figure 1 α-smooth muscle actin and smoothelin expression in a cutaneous hypertrophic scar. A: Following a burn injury, a retractile hypertrophic scar was observed (from Vincent Casoli, Plastic Surgery and Burns Unit, University Hospital of Bordeaux, France); B: Hematoxylin and eosin staining shows typical hypertrophic scar architecture with nodules (N) surrounded by cell bundles (CB); C: α-smooth muscle actin is expressed in vascular smooth muscle cells and myofibroblasts both in and around the nodules; D: Smoothelin is only expressed by vascular tunica media smooth muscle cells.

Figure 2 α-smooth muscle actin and smoothelin expression in normal, fibrotic and cirrhotic livers. A and B: In the normal liver, α-smooth muscle actin (A) and smoothelin (B) show similar expression in tunica media smooth muscle cells of the portal arteries and veins and in the centrilobular veins; C and D: In severe fibrosis, myofibroblasts express high amounts of α-smooth muscle actin (C), while smoothelin is only expressed at low levels (D) (α-smooth muscle actin and smoothelin are coexpressed in vascular smooth muscle cells); E and F: In the cirrhotic liver, myofibroblasts express α-smooth muscle actin in fibrotic septae (E) and numerous myofibroblasts also express smoothelin (F); however, smoothelin expression is lower compared with α-smooth muscle actin expression (insert). α-smooth muscle actin and smoothelin are co-expressed in vascular tunica media smooth muscle cells (F).

Figure 3 Cellular co-localization of α-smooth muscle actin and smoothelin in a fibrotic liver. A: α-smooth muscle actin expression (green); B: Smoothelin expression (red); C: Merged (nuclei are stained with DAPI). Smoothelin-expressing cells also express α-smooth muscle actin.

Figure 4 α-Smooth muscle actin and smoothelin expression in hepatocellular carcinoma. A and B: α-smooth muscle actin (A) and smoothelin (B) are expressed similarly in the stroma reaction surrounding the tumor (arrows) and around tumoral hepatocytes; C and D: α-smooth muscle actin (C) and smoothelin (D) are expressed by pericyte-like cells underlying capillaries between tumoral hepatocytes.