Thrombospondin-1 induces Sinusoidal Endothelial Cell Defenestration

摘要

We find that TSP1 causes contraction and closure of LSEC fenestrae through CD47 receptor signaling. Plasmin reverses the effects of TSP, and may help explain the effectiveness of plasmin-promoting anti-fibrotic therapies such as anti-PAI1 therapy or HGF gene therapy . Anti-fibrotic therapies that target TSP1, through cleavage or other mechanisms, may have beneficial effects on LSEC and sinusoidal function, in addition to known effects on TGF-beta cytokine signaling.