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Dig Dis Sci (2010) 55:496504 DOI 10.1007/s10620-009-0919-9
ORIGINAL ARTICLE
Hepatic Stellate Cell and Myobroblast-Like Cell Gene Expression in the Explanted Cirrhotic Livers of Patients Undergoing Liver Transplantation
J. Michael Estep Linda OReilly Geraldine Grant James Piper Johann Jonsson Arian Afendy Vikas Chandhoke Zobair M. Younossi
Received: 27 April 2009 / Accepted: 9 July 2009 / Published online: 13 August 2009 Springer Science+Business Media, LLC 2009
AbstractBackground Hepatic stellate cells (HSC) are involved in hepatic brogenesis. Cell signaling associated with an insult to the liver affects an HSC transdifferentiation to brogenic myobroblast-like cells.
Aims To investigate the transcriptional expression distinguishing HSC and myobroblast-like cells between livers with and without cirrhosis.
Methods Tissue from ten cirrhotic livers (undergoing transplant) and four non-cirrhotic livers from the National Disease Research Interchange underwent cell separation to extract HSC and myobroblast-like cell populations. Separated cell types as well as LI-90 cells were subjected to microarray analysis. Selected microarray results were veried by quantitative real-time PCR.
Results Differential expression of some genes, such as IL-1b, IL-1a, and IL-6, was associated with both trans-differentiation and disease. Other genes, such as fatty acid 2-hydroxylase only show differential expression in association with disease. Functional analysis supported these ndings, indicating some signal transduction pathways
(IL-6) are involved in disease and activation, whereas retinoid X receptor signaling in HSC from cirrhotic and non-cirrhotic livers varies in scope and quality. Conclusions These ndings indicate distinct phenotypes for HSC from cirrhotic and non-cirrhotic livers. Furthermore, coordinated differential expression between genes involved in the same signal transduction pathways provides some insight into the mechanisms that may control the balance between brogenesis and brolysis.
Keywords Cirrhosis Stellate cells Inammation
Gene expression Myobroblast-like cell
Introduction
The progression of hepatic brosis into cirrhosis is a serious sequela of chronic liver disease. Patients with cirrhosis can develop complications such as ascites and hepatocelluar carcinoma that can negatively affect survival and lead to liver transplantation. In 2007, according to data gathered by the United Network for Organ Sharing, there are 16,732 people waiting for liver transplants in the US alone, many of whom will die waiting or became too sick to receive a liver transplant [1]. Cirrhosis is the seventh leading cause of disease-related death in the United States. Although there is increasing and...