Targeting hepatic stellate cells to prevent or reverse liver fibrosis

Activation of stellate cells as a target for the treatment of liver fibrosisIn his thesis, Zhang introduces the crucial role of hepatic stellate cell activation in the development of liver fibrosis. Activated liver stellate cells are the main precursors of myofibroblasts. Therapy targeting hepatic stellate cells can prevent or reverse liver fibrosis.The aging ("senescence") of hepatic stellate cells is interpreted as a mechanism that protects against the progression of liver fibrosis. The biomarkers, signaling pathways and likely effects of hepatic stellate cell senescence are explained. Zhang proposes that the biomarkers P21 (cell cycle arrest), senescence-associated β-galactosidase (lysosomal galactosidase), and interleukin-6 (senescence-associated secretory phenotype) can be used to identify senescent hepatic stellate cells. Although the senescence of liver stellate cells has not yet been fully elucidated, therapy-induced senescence of hepatic stellate cells, followed by senolytics, may be an optimal strategy for combating liver fibrosis.Esculetin, a coumarin derivative, has also been shown to cause the senescence of hepatic stellate cells. It appears that in senescent hepatic stellate cells, collagen production and cell proliferation are reduced. In addition, senescent hepatic stellate cells develop resistance to a return to active proliferation.