UC San Diego

Hepatic Stellate Cells (HSC) remain quiescent in a healthy liver but undergo an activation process in response to liver injury. Once activated, HSC begin to produce and export collagen rich, fibrous deposits into the extracellular space. This process, known as extracellular matrix (ECM) synthesis, begins to change the histology of the liver resulting in the condition of liver fibrosis. HSC only produce this “liver scarring”, otherwise known as fibrogenesis, in their activated state. As injury persists, fibrosis advances and eventually begins to impede on hepatic function by blocking blood flow to hepatocytes, causing liver cirrhosis, which is end stage fibrosis. The fibrotic response results from liver injury of all forms. Other than a liver transplant, there is currently no treatment for liver fibrosis/cirrhosis.This report chronicles the efficacy and safety assays of peptides developed from a phosphorylation site, tetrapeptides, that are effective in inducing apoptosis in activated HSC via inhibition of survival pathways shown previously to be critical for the development of liver fibrosis. Also outlined; development of the peptides for in-vivo treatment shown effective in not only stopping fibrogenic progression but inducing the regression of liver fibrosis.