Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential

Figure 4

Step-by-step therapy using HGF in a chronology of septic phases including infection, SIRS, coagulation, and MOF. HGF inhibits the development of sepsis-induced MOF through different ways at different phases. (a) In an initial step, HGF targets endotoxin-primed macrophages and inhibits cytokine storm via indirect (i.e., HO-1 recruitment) and direct (i.e., GSK3β inactivation) pathways [29, 46]; (b) in an early step (i.e., post-cytokine storm), HGF protects endothelial cells from cytokine-induced inflammatory events, such as ICAM-1 and E-selectin overexpressions [32–34], and HGF also prevents DIC via the preservation of thrombomodulin on endothelial cells [44, 45]; (c) in a middle step (i.e., after coagulation), HGF protects resident functional cells from hypoxia or cytokines via early induction of Bcl-xL or Bcl-2 [40]; finally (d) in an advanced stage (i.e., after injury), HGF enhances tissue repair via enhancing mitogenesis and morphogenesis of surviving epithelial cells [10, 15].