Chitinase 3-like-1 Promotes Intrahepatic Activation of Coagulation Through Induction of Tissue Factor in Mice

Abstract

Coagulation is a critical component in the progression of liver disease. Identification of key molecules involved in the intrahepatic activation of coagulation (IAOC) will be instrumental in the development of effective therapies against liver disease. Using a mouse model of concanavalin A (Con A)-induced hepatitis, in which IAOC plays an essential role in causing liver injury, we uncovered a previously unknown procoagulant function of chitinase 3 like 1 (Chi3l1). Chi3l1 expression is dramatically elevated after Con A challenge, which is dependent on Con A-induced T cell activation, and the resulting IFN-γ and TNF-α productions. Compared to wild type mice, Chi3l1^-/- mice show less IAOC, reduced tissue factor (TF) expression and attenuated liver injury. Reconstituting Chi3l1^-/- mice with recombinant TF triggers IAOC and augments liver injury. Conclusion: Our data demonstrate that Chi3l1, through induction of TF via MAPK activation, promotes IAOC and tissue injury. This article is protected by copyright. All rights reserved.

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