| Expression profiling of fibroblasts identifies cell cycle abnormalities in schizophrenia. | |
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MedLine Citation:
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PMID: 19916557 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Many previous studies have attempted to gain insight into the underlying pathophysiology of schizophrenia by studying postmortem brain tissues of schizophrenia patients. However, such analyses can be confounded by artifactual features of this approach such as lengthy agonal state and postmortem interval times. As several aspects of schizophrenia are also manifested at the peripheral level in proliferating cell types, we have studied the disorder through systematic transcriptomic and proteomic analyses of skin fibroblasts biopsied from living patients. We performed comparative transcriptomic and proteomic profiling to characterize skin fibroblasts from schizophrenia patients compared to healthy controls. Transcriptomic profiling using cDNA array technology showed that pathways associated with cell cycle regulation and RNA processing were altered in the schizophrenia subjects (n = 12) relative to controls (n = 12). LC-MS(E) proteomic profiling led to identification of 16 proteins that showed significant differences in expression between schizophrenia (n = 11) and control (n = 11) subjects. Analysis in silico revealed that these proteins were also associated with proliferation and cell growth pathways. To validate these findings at the protein level, fibroblast protein extracts were analyzed by Western blotting which confirmed the differential expression of three key proteins associated with these pathways. At the functional level, we confirmed the decreased proliferation phenotype by showing that cultured fibroblasts from schizophrenia subjects (n = 5) incorporated less (3)H-thymidine into their nuclei compared to those from controls (n = 6) by day 4 over an 8 day time course study. Similar abnormalities in cell cycle and growth pathways have been reported to occur in the central nervous system in schizophrenia. These studies demonstrate that fibroblasts obtained from living schizophrenia subjects show alterations in cellular proliferation and growth pathways. Future studies aimed at characterizing such pathways in fibroblasts and other proliferating cell types from schizophrenia patients could elucidate the molecular mechanisms associated with the pathophysiology of schizophrenia and provide a useful model to support drug discovery efforts. |
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Authors:
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L Wang; H E Lockstone; P C Guest; Y Levin; A Palot?s; S Pietsch; E Schwarz; H Rahmoune; L W Harris; D Ma; S Bahn |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of proteome research Volume: 9 ISSN: 1535-3907 ISO Abbreviation: J. Proteome Res. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-04 Completed Date: 2010-03-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101128775 Medline TA: J Proteome Res Country: United States |
Other Details:
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Languages: eng Pagination: 521-7 Citation Subset: IM |
Affiliation:
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Institute of Biotechnology, University of Cambridge, Cambridge, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Cell Cycle / genetics Cell Growth Processes / physiology Cells, Cultured Chromatography, Liquid Computer Simulation Fibroblasts / metabolism* Gene Expression Profiling / methods* Humans Male Mass Spectrometry Middle Aged Oligonucleotide Array Sequence Analysis Proteomics / methods* Reproducibility of Results Schizophrenia / genetics*, metabolism, pathology* |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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