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Expression profiling of fibroblasts identifies cell cycle abnormalities in schizophrenia
L Wang1, H E Lockstone, P C Guest
1Institute of Biotechnology, University of Cambridge, Cambridge, UK.
Journal of Proteome Research
|November 18, 2009
Summary
Schizophrenia research using skin fibroblasts reveals altered cell proliferation and growth pathways. These findings in living patients offer a new model for understanding schizophrenia pathophysiology and drug discovery.
Area of Science:
- Cell Biology
- Neuroscience
- Genomics & Proteomics
Background:
- Postmortem brain tissue studies of schizophrenia are limited by confounding factors like agonal state and postmortem interval.
- Schizophrenia pathophysiology may involve peripheral manifestations in proliferating cell types.
- Skin fibroblasts offer a viable peripheral model for studying schizophrenia in living patients.
Purpose of the Study:
- To investigate schizophrenia pathophysiology using transcriptomic and proteomic analyses of skin fibroblasts from living patients.
- To compare molecular and functional profiles of fibroblasts from schizophrenia patients and healthy controls.
Main Methods:
- Comparative transcriptomic profiling using cDNA array technology.
- Proteomic profiling using Liquid Chromatography-Mass Spectrometry (LC-MS(E)).
- Western blotting for protein validation and functional assays (e.g., (3)H-thymidine incorporation) to assess cell proliferation.
Main Results:
- Transcriptomic analysis revealed altered cell cycle regulation and RNA processing pathways in schizophrenia fibroblasts.
- Proteomic analysis identified 16 differentially expressed proteins associated with proliferation and cell growth pathways.
- Functional assays confirmed decreased fibroblast proliferation in schizophrenia subjects compared to controls.
Conclusions:
- Skin fibroblasts from schizophrenia patients exhibit significant alterations in cellular proliferation and growth pathways.
- These findings suggest fibroblasts can serve as a valuable peripheral model for schizophrenia research.
- Further studies on fibroblast pathways may elucidate schizophrenia mechanisms and support drug discovery efforts.
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