Erschienen in:
01.02.2010 | Original Article
Hepatic Stellate Cell and Myofibroblast-Like Cell Gene Expression in the Explanted Cirrhotic Livers of Patients Undergoing Liver Transplantation
verfasst von:
J. Michael Estep, Linda O’Reilly, Geraldine Grant, James Piper, Johann Jonsson, Arian Afendy, Vikas Chandhoke, Zobair M. Younossi
Erschienen in:
Digestive Diseases and Sciences
|
Ausgabe 2/2010
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Abstract
Background
Hepatic stellate cells (HSC) are involved in hepatic fibrogenesis. Cell signaling associated with an insult to the liver affects an HSC transdifferentiation to fibrogenic myofibroblast-like cells.
Aims
To investigate the transcriptional expression distinguishing HSC and myofibroblast-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 myofibroblast-like cell populations. Separated cell types as well as LI-90 cells were subjected to microarray analysis. Selected microarray results were verified by quantitative real-time PCR.
Results
Differential expression of some genes, such as IL-1β, IL-1α, and IL-6, was associated with both transdifferentiation and disease. Other genes, such as fatty acid 2-hydroxylase only show differential expression in association with disease. Functional analysis supported these findings, 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 findings 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 fibrogenesis and fibrolysis.