Hepatic stellate cells express functional CXCR4

• DOI: 10.1002/hep.22890
• Publication Date: 2009-02-09T15:42:33Z
• Authors: Feng Hong; Ana Tuyama; Ting Fang Lee; Johnny Loke; Ritu Agarwal; Xin Cheng; Anita Garg; M. Isabel Fiel; Myron Schwartz; Jose Walewski; Andrea Branch; Alison D. Schecter; Meena B. Bansal
• Keywords: Hepatic stellate cell; CXC chemokine receptors

Chemokine interactions with their receptors have been implicated in hepatic stellate cell (HSC) activation. The expression of CXCR4 messenger RNA is increased hepatitis C cirrhotic livers and plasma levels its endogenous ligand, stromal cell-derived factor-1alpha (SDF-1alpha), correlate fibrosis these patients. by HSCs has not reported. We therefore examined whether express vivo vitro explored SDF-1alpha/CXCR4 receptor engagement promotes HSC activation, fibrogenesis, proliferation. protein both SDF-1alpha immunoflourescent immunohistochemical staining confirms that vivo. Immortalized human cells as well primary CXCR4, surface increases progressive culture-induced Treatment recombinant alpha-smooth muscle actin collagen I stimulates a dose-dependent increase Inhibitor studies suggest SDF-1alpha/CXCR4-dependent extracellular signal-regulated kinase 1/2 Akt phosphorylation mediate effects on proliferation.HSCs vitro. activation profibrogenic through Extracellular phosphoinositide 3-kinase pathways SDF-1alpha-induced availability small molecule inhibitors make this an appealing target for antifibrotic approaches.