Figure 1.

Simplified model of liver-specific cellular events in radiation-induced liver injury. (a) In the normal liver, liver sinusoids are lined with SECs and KCs. Quiescent hepatic stellate cells (qHSCs) are located in the space of Disse and are in close contact with HCs and SECs. (b) In the irradiated liver, ① injured SECs undergo apoptosis and release TNF-α, which promotes HC apoptosis and KC activation. ② In addition, injured SECs induce the penetration of red blood cells (RBCs) and activate fibrin deposition in central veins (CVs), leading to sinusoidal obstruction. ③ The ensuing hypoxic environment leads to the death of HCs and the activation of KCs. ④ Activated KCs release TGF-β, the major profibrogenic cytokine, which promotes the transdifferentiation of qHSCs into MF-HSCs. ⑤ Apoptotic HCs produce Hh ligands, which trigger the proliferation of Hh-responsive cells, such as HSCs. MF-HSCs accumulate and promote the deposition of extracellular matrix proteins, leading to liver fibrosis in the late stage of RILD.