IMR Press / FBL / Volume 7 / Issue 4 / DOI: 10.2741/reeves

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article

Activation of hepatic stellate cells – a key issue in liver fibrosis

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1 Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029-6574, USA
Front. Biosci. (Landmark Ed) 2002, 7(4), 808–826; https://doi.org/10.2741/reeves
Published: 1 April 2002
Abstract

Hepatic fibrosis describes the presence of excess collagen due to new fiber formation, laid down as part of the tissue repair response to chronic liver injury. The causes of injury include toxins, disorders of the immune system, viral and parasitic infections, as well as rarer liver diseases such as haemochromatosis, Wilson's disease and galactosaemia. Whatever the cause of injury, the cells and soluble factors contributing to this wound healing response are similar. The principal effector of hepatic fibrogenesis is now widely recognized as the hepatic stellate cell. Stellate cells are usually quiescent cells, but in response to liver injury they undergo an activation process in which they become highly proliferative and synthesize a fibrotic matrix rich in type I collagen. Initiation of stellate cell activation is largely due to paracrine stimulation, whereas perpetuation of activation involves autocrine as well as paracrine loops, and is dependent on a number of functional changes. The principal paracrine and autocrine factors currently thought to be involved in these processes are discussed in this review, as are the roles of the extracellular matrix, the nuclear receptor superfamily, non-peptide ligands, and oxidative stress.

Keywords
Liver
fibrosis
hepatic stellate cell
platelet derived growth factor
extracellular matrix
Kupffer cell
leptin
transforming growth factor beta
tumor necrosis factor alpha
Review
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