Hepatic stellate cell and myofibroblast-like cell gene expression in the explanted cirrhotic livers of patients undergoing liver transplantation.
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.


OBJECTIVE
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-1beta, IL-1alpha, 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.
Estep
J Michael
JM
Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA.
O'Reilly
Linda
L
Grant
Geraldine
G
Piper
James
J
Jonsson
Johann
J
Afendy
Arian
A
Chandhoke
Vikas
V
Younossi
Zobair M
ZM
D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053582:Interleukin-1alpha / Q000096:biosynthesis / Q000235:genetics*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D004247:DNA
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