Fibrogenesis. Increased matrix production is the most direct way that stellate cell activation generates hepatic fibrosis. The most potent stimulus to collagen I production is TGF-beta, which is derived from both paracrine and autocrine sources.
Lipid peroxidation products are emerging as important stimuli to ECM production; their effects may be amplified by loss of antioxidant capacity of stellate cells as they activate.[30] These important insights have provoked efforts to use antioxidants as therapy for hepatic fibrosis (see section on Therapy of Hepatic Fibrosis, below)