Gene profiling of scleroderma skin reveals robust signatures of disease that are imperfectly reflected in the transcript profiles of explanted fibroblasts.
OBJECTIVE: To determine whether biopsy specimens obtained from systemic sclerosis (SSc) lesions show a distinctive gene profile, whether that gene profile is maintained in fibroblasts cultured from SSc skin biopsy specimens, and whether results from tissue obtained from multiple clinical centers can...
| Published in: | Arthritis & Rheumatism Vol. 54; no. 6; pp. 1961 - 1974 |
|---|---|
| Main Authors: | , , , , , , , , , , , |
| Format: | pictorial research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
2006 Jun
|
| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=106133086&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 106133086 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00043591 04N jtl: Arthritis & Rheumatism issn: 00043591 maglogo: Y pubinfo: dt: 2006 Jun vid: 54 iid: 6 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 106133086 106133086 2009213874 10.1002/art.21894 NLM16736506 106133086 ppf: 1961 ppct: 13 formats: tig: atl: Gene profiling of scleroderma skin reveals robust signatures of disease that are imperfectly reflected in the transcript profiles of explanted fibroblasts. aug: au: Gardner H Shearstone JR Bandaru R Crowell T Lynes M Trojanowska M Pannu J Smith E Jablonska S Blaszczyk M Tan FK Mayes MD affil: Biogen Idec, Cambridge, Massachusetts. sug: subj: Fibroblasts Genetic Techniques Scleroderma, Systemic Skin Adult Biopsy Data Analysis Software Female Glycoproteins Metabolism Growth Substances Metabolism Immunohistochemistry Male Middle Age Phenotype Proteins Metabolism Texas Human Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: OBJECTIVE: To determine whether biopsy specimens obtained from systemic sclerosis (SSc) lesions show a distinctive gene profile, whether that gene profile is maintained in fibroblasts cultured from SSc skin biopsy specimens, and whether results from tissue obtained from multiple clinical centers can be combined to yield useful observations in this rare disease. METHODS: Biopsy samples and passaged fibroblasts were stored in RNAlater solution prior to processing for RNA. RNA from SSc and control skin biopsy specimens, as well as SSc and control explanted passage 4 fibroblasts, from 9 patients and 9 controls was hybridized to Affymetrix HG-U133A arrays. Data were analyzed using the BRB ArrayTools system. When appropriate, findings were followed up with immunohistochemical analysis or TaqMan studies. RESULTS: Biopsy samples obtained from patients with SSc had a robust and distinctive gene profile, with approximately 1,800 qualifiers distinguishing normal skin from SSc skin at a significant level. The SSc phenotype was the major driver of sample clusters, independent of origin. Alterations in transforming growth factor beta and Wnt pathways, extracellular matrix proteins, and the CCN family were prominent. Explanted fibroblasts from SSc biopsy samples showed a far smaller subset of changes that were relatively variable between samples, suggesting that either nonfibroblast cell types or other aspects of the dermal milieu are required for full expression of the SSc phenotype. CONCLUSION: SSc has a distinct gene profile that is not confounded by geographic location, indicating that extended multicenter studies may be worthwhile to identify distinct subsets of disease by transcript profiling. Explanted SSc fibroblasts show an incomplete reflection of the SSc phenotype. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|