Transdifferentiation of hepatic stellate cells (Ito cells) to myofibroblasts: a key event in hepatic fibrogenesis

A M Gressner
Kidney International. Supplement 1996, 54: S39-45
Hepatic stellate cells (HSC) are the major source of extracellular matrix components (ECM), if these precursor cells are activated in areas of necroinflammation to proliferate and to transdifferentiate from the retinoid storing to the ECM-producing phenotype termed myofibroblast (MFB). The mechanisms of HSC activation are crucial for the understanding of liver fibrogenesis. Activation is promoted by cytokines from Kupffer cells (KC) and platelets, of which TGF-beta is of great importance. It stimulates in HSC gene expression of ECM molecules but inhibits proliferation and induces phenotypic transdifferentiation. Latent TGF-beta is activated in cooperation with endothelial cells. TGF-alpha, also secreted by KC, stimulates HSC proliferation. In addition, hepatocytes (PC) enhance proliferation of HSC but ECM production is not affected. The mitogenic effect is mediated by TGF-alpha, IGF-1 and other cytokines. The paracrine signals of PC are increased by PC damage. During transdifferentiation MFB increasingly express TGF-beta and TGF-alpha, which are suspected to be involved in autocrine stimulation of MFB and paracrine activation of still untransformed HSC. A three-step cascade model of HSC activation is suggested. A preinflammatory phase initiates HSC activation by discharge of mitogenic cytokines (TGF-alpha, IGF-1) from damaged PC followed by the inflammatory phase based on cytokines (TGF-beta, etc.) from activated KC. In the postinflammatory phase MFB are stimulated by autocrine mechanisms contributing potentially to a perpetuation of the fibrogenic process even after cessation of the primary event (PC damage).

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"