Figure 9.

Proposed time course of the effect of Pdgfra loss in hepatic stellate cells (HSCs) during carbon tetrachloride–induced chronic liver injury in mice. During the early stages of chronic hepatocyte injury, Pdgfra loss from HSCs leads to modest reduction in fibrosis likely as a result of impaired HSC proliferation and migration. As chronic liver injury progresses, HSCs and myofibroblasts without Pdgfra are susceptible to cell death, which in turn leads to increased inflammatory cells and hepatic macrophages, likely because of proinflammatory cell debris and chemokines released from dying HSCs and myofibroblasts. The resulting influx of phagocytic hepatic macrophages improves clearing of necrotic hepatocytes near injury foci, ameliorating overall liver injury. ALT, alanine transaminase; AST, aspartate transaminase; PDGF, platelet-derived growth factor.