Cytokine receptors and signaling in hepatic stellate cells

Following acute or chronic liver tissue damage, hepatic stellate cells (HSC s) undergo a process of activation toward a phenotype characterized by incr eased proliferation, motility, contractility, and synthesis of extracellula r matrix components. Activation of HSCs is regulated by several soluble fac tors, including growth factors, cytokines, chemokines, and products of oxid ative stress, as well as by extensive changes in the composition and organi zation of the ECM. Different groups of soluble factors may be classified ac cording to their prevalent biological effect: (a) factors promoting HSC pro liferation and/or migration (i.e., platelet-derived growth factor, basic fi broblast growth factor, insulin-like growth factor-1); (b) factors promotin g fibrillar ECM accumulation, particularly transforming growth factor-beta1 ; (c) factors with a prevalent contractile effect on HSCs, such as endothel in-1, thrombin, angiotensin-Il and vasopressin, although all these agents a lso may promote HSC proliferation; (d) proinflammatory cytokines and chemok ines; and (e) cytokines with a prominent antiinflammatory/antifibrogenic ac tivity, such as interleukin-10 and interferon-gamma. Additional important i ssues are represented by the relationship between cytokine and integrin sig naling, and by the effects of oxidative stress-related molecules on cytokin e signaling. In the past decade the major intracellular signaling pathways elicited by these factors in HSCs have been greatly elucidated.