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Novel perspectives on the origins of the hepatic myofibroblasts

Authors Xu J, Liu X, Brenner D, Kisseleva T

Received 18 December 2014

Accepted for publication 13 January 2015

Published 20 March 2015 Volume 2015:7 Pages 111—119


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Denis Wirtz

Jun Xu,1,2 Xiao Liu,1,2 David A Brenner,1 Tatiana Kisseleva2

1Department of Medicine, 2Department of Surgery, University of California, San Diego, CA, USA

Abstract: Liver fibrosis results from chronic liver injury that causes hepatocellular damage. Damaged hepatocytes apoptose, and release factors that facilitate recruitment of leukocytes to the site of injury, which in turn mediate recruitment and activation of liver- resident (Kupffer cells) and bone marrow (BM)-derived macrophages. Activated macrophages secrete TGF-ß1, the major profibrogenic cytokine, which activates hepatic myofibroblasts, which are not present in the liver under physiological conditions. Several sources of myofibroblasts have been identified, but it is believed that liver-resident hepatic stellate cells (HSCs) and portal fibroblasts (PFs) are the major source of hepatic myofibroblasts in fibrotic liver. Fibrocytes, designated as BM-derived collagen Type I producing cells, were also implicated in liver fibrosis; hence, their contribution to liver fibrosis remains controversial. Upon removal of the etiological agent, myofibroblasts either undergo apoptosis or inactivate into a quiescent-like state, followed by resorbtion of the fibrous scar. However, prolonged/repeated liver injury triggers irreversible cross-linking of collagen fibers that prevents fibrous scar from collagenase-mediated degradation. This review will discuss several types of fibrogenic cells contributing to the myofibroblast population, and the signaling pathways regulating their activation and collagen deposition.

Keywords: Liver fibrosis, TGF-ß1 signaling, hepatic stellate cells, portal fibroblasts, fibrocytes, collagen Type I deposition

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