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Erschienen in: Digestive Diseases and Sciences 2/2010

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.
Literatur
2.
Zurück zum Zitat Iredale JP. Cirrhosis: New research provides a basis for rational and targeted treatments. BMJ. 2003;327(7407):143–147.CrossRefPubMed Iredale JP. Cirrhosis: New research provides a basis for rational and targeted treatments. BMJ. 2003;327(7407):143–147.CrossRefPubMed
3.
Zurück zum Zitat Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem. 2000;275(4):2247–2250.CrossRefPubMed Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem. 2000;275(4):2247–2250.CrossRefPubMed
4.
Zurück zum Zitat Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28(4):370–379. (Epub 2008 Oct 27).CrossRefPubMed Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28(4):370–379. (Epub 2008 Oct 27).CrossRefPubMed
5.
Zurück zum Zitat Blaner WS, O’Byrne SM, Wongsiriroj N, Kluwe J, D’Ambrosio DM, Jiang H, Schwabe RF, Hillman EM, Piantedosi R, Libien J. Hepatic stellate cell lipid droplets: A specialized lipid droplet for retinoid storage. Biochim Biophys Acta. 2009;1791(6):467–473. (Epub 2008 Nov 24).PubMed Blaner WS, O’Byrne SM, Wongsiriroj N, Kluwe J, D’Ambrosio DM, Jiang H, Schwabe RF, Hillman EM, Piantedosi R, Libien J. Hepatic stellate cell lipid droplets: A specialized lipid droplet for retinoid storage. Biochim Biophys Acta. 2009;1791(6):467–473. (Epub 2008 Nov 24).PubMed
6.
Zurück zum Zitat Van Rossen E, Vander Borght S, van Grunsven LA, et al. Vinculin and cellular retinol-binding protein-1 are markers for quiescent and activated hepatic stellate cells in formalin-fixed paraffin embedded human liver. Histochem Cell Biol. 2009;131(3):313–325. (Epub 2008 Dec 4).CrossRefPubMed Van Rossen E, Vander Borght S, van Grunsven LA, et al. Vinculin and cellular retinol-binding protein-1 are markers for quiescent and activated hepatic stellate cells in formalin-fixed paraffin embedded human liver. Histochem Cell Biol. 2009;131(3):313–325. (Epub 2008 Dec 4).CrossRefPubMed
7.
Zurück zum Zitat Lalazar A, Wong L, Yamasaki G, Friedman SL. Early genes induced in hepatic stellate cells during wound healing. Gene. 1997;195(2):235–243.CrossRefPubMed Lalazar A, Wong L, Yamasaki G, Friedman SL. Early genes induced in hepatic stellate cells during wound healing. Gene. 1997;195(2):235–243.CrossRefPubMed
8.
Zurück zum Zitat Geerts A. History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin Liver Dis. 2001;21(3):311–335.CrossRefPubMed Geerts A. History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin Liver Dis. 2001;21(3):311–335.CrossRefPubMed
9.
Zurück zum Zitat Friedman SL. Hepatic fibrosis–overview. Toxicology. 2008;254(3):120–129. (Epub 2008 Jul 10).CrossRefPubMed Friedman SL. Hepatic fibrosis–overview. Toxicology. 2008;254(3):120–129. (Epub 2008 Jul 10).CrossRefPubMed
10.
Zurück zum Zitat Friedman SL. Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies. N Engl J Med. 1993;328(25):1828–1835.CrossRefPubMed Friedman SL. Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies. N Engl J Med. 1993;328(25):1828–1835.CrossRefPubMed
11.
Zurück zum Zitat Gorreta F, Barzaghi D, VanMeter AJ, Chandhoke V, Del Giacco L. Development of a new reference standard for microarray experiments. Biotechniques. 2004;36(6):1002–1009.PubMed Gorreta F, Barzaghi D, VanMeter AJ, Chandhoke V, Del Giacco L. Development of a new reference standard for microarray experiments. Biotechniques. 2004;36(6):1002–1009.PubMed
12.
Zurück zum Zitat Issa R, Williams E, Trim N, et al. Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors. Gut. 2001;48(4):548–557.CrossRefPubMed Issa R, Williams E, Trim N, et al. Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors. Gut. 2001;48(4):548–557.CrossRefPubMed
13.
Zurück zum Zitat Son G, Iimuro Y, Seki E, Hirano T, Kaneda Y, Fujimoto J. Selective inactivation of NF-kappaB in the liver using NF-kappaB decoy suppresses CCl4-induced liver injury and fibrosis. Am J Physiol Gastrointest Liver Physiol. 2007;293(3):G631–G639. (Epub 2007 Jul 19).CrossRefPubMed Son G, Iimuro Y, Seki E, Hirano T, Kaneda Y, Fujimoto J. Selective inactivation of NF-kappaB in the liver using NF-kappaB decoy suppresses CCl4-induced liver injury and fibrosis. Am J Physiol Gastrointest Liver Physiol. 2007;293(3):G631–G639. (Epub 2007 Jul 19).CrossRefPubMed
Metadaten
Titel
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
Publikationsdatum
01.02.2010
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 2/2010
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-009-0919-9

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