Systemic and Cell Type-specific Gene Expression Patterns in Scleroderma Skin

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Oct 8

PMID 14530402

Citations 179

Authors

Michael L Whitfield

Deborah R Finlay

John Isaac Murray

Olga G Troyanskaya

Jen-Tsan Chi

Alexander Pergamenschikov

Timothy H McCalmont

Patrick O Brown

David Botstein

M Kari Connolly

Affiliations

Soon will be listed here.

Abstract

We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma. We found consistent differences in the patterns of gene expression between skin biopsies from individuals with scleroderma and those from normal, unaffected individuals. The biopsies from affected individuals showed nearly indistinguishable patterns of gene expression in clinically affected and clinically unaffected tissue, even though these were clearly distinguishable from the patterns found in similar tissue from unaffected individuals. Genes characteristically expressed in endothelial cells, B lymphocytes, and fibroblasts showed differential expression between scleroderma and normal biopsies. Analysis of lymphocyte populations in scleroderma skin biopsies by immunohistochemistry suggest the B lymphocyte signature observed on our arrays is from CD20+ B cells. These results provide evidence that scleroderma has systemic manifestations that affect multiple cell types and suggests genes that could be used as potential markers for the disease.

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References

Alizadeh A, Eisen M, Davis R, Ma C, Lossos I, Rosenwald A . Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000; 403(6769):503-11. DOI: 10.1038/35000501. View

Perou C, Jeffrey S, van de Rijn M, Rees C, Eisen M, Ross D . Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci U S A. 1999; 96(16):9212-7. PMC: 17759. DOI: 10.1073/pnas.96.16.9212. View

Ashburner M, Ball C, Blake J, Botstein D, Butler H, Cherry J . Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000; 25(1):25-9. PMC: 3037419. DOI: 10.1038/75556. View

Steen V, Medsger Jr T . Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum. 2000; 43(11):2437-44. DOI: 10.1002/1529-0131(200011)43:11<2437::AID-ANR10>3.0.CO;2-U. View

Pruitt K, Maglott D . RefSeq and LocusLink: NCBI gene-centered resources. Nucleic Acids Res. 2000; 29(1):137-40. PMC: 29787. DOI: 10.1093/nar/29.1.137. View

Sherlock G, Hernandez-Boussard T, Kasarskis A, Binkley G, Matese J, Dwight S . The Stanford Microarray Database. Nucleic Acids Res. 2000; 29(1):152-5. PMC: 29818. DOI: 10.1093/nar/29.1.152. View

Tusher V, Tibshirani R, Chu G . Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001; 98(9):5116-21. PMC: 33173. DOI: 10.1073/pnas.091062498. View

Fisk H, Winey M . The mouse Mps1p-like kinase regulates centrosome duplication. Cell. 2001; 106(1):95-104. DOI: 10.1016/s0092-8674(01)00411-1. View

Sorlie T, Perou C, Tibshirani R, Aas T, Geisler S, Johnsen H . Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001; 98(19):10869-74. PMC: 58566. DOI: 10.1073/pnas.191367098. View

10.

Cabral C, Liu Y, Sifers R . Dissecting glycoprotein quality control in the secretory pathway. Trends Biochem Sci. 2001; 26(10):619-24. DOI: 10.1016/s0968-0004(01)01942-9. View

11.

Zhou X, Tan F, Xiong M, Milewicz D, Feghali C, Fritzler M . Systemic sclerosis (scleroderma): specific autoantigen genes are selectively overexpressed in scleroderma fibroblasts. J Immunol. 2001; 167(12):7126-33. DOI: 10.4049/jimmunol.167.12.7126. View

12.

Cowper S, Su L, Bhawan J, Robin H, Leboit P . Nephrogenic fibrosing dermopathy. Am J Dermatopathol. 2002; 23(5):383-93. DOI: 10.1097/00000372-200110000-00001. View

13.

Ferri C, Valentini G, Cozzi F, Sebastiani M, Michelassi C, La Montagna G . Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore). 2002; 81(2):139-53. DOI: 10.1097/00005792-200203000-00004. View

14.

Joyal F, Raynauld J, Roussin A, Rich E, Goulet J, Raymond Y . Predicting mortality in systemic sclerosis: analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Medicine (Baltimore). 2002; 81(2):154-67. DOI: 10.1097/00005792-200203000-00005. View

15.

Saito E, Fujimoto M, Hasegawa M, Komura K, Hamaguchi Y, Kaburagi Y . CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse. J Clin Invest. 2002; 109(11):1453-62. PMC: 150999. DOI: 10.1172/JCI15078. View

16.

Whitfield M, Sherlock G, Saldanha A, Murray J, Ball C, Alexander K . Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell. 2002; 13(6):1977-2000. PMC: 117619. DOI: 10.1091/mbc.02-02-0030. View

17.

Leask A, Abraham D, Finlay D, Holmes A, Pennington D, Shi-Wen X . Dysregulation of transforming growth factor beta signaling in scleroderma: overexpression of endoglin in cutaneous scleroderma fibroblasts. Arthritis Rheum. 2002; 46(7):1857-65. DOI: 10.1002/art.10333. View

18.

Chang H, Chi J, Dudoit S, Bondre C, van de Rijn M, Botstein D . Diversity, topographic differentiation, and positional memory in human fibroblasts. Proc Natl Acad Sci U S A. 2002; 99(20):12877-82. PMC: 130553. DOI: 10.1073/pnas.162488599. View

19.

Troyanskaya O, Garber M, Brown P, Botstein D, Altman R . Nonparametric methods for identifying differentially expressed genes in microarray data. Bioinformatics. 2002; 18(11):1454-61. DOI: 10.1093/bioinformatics/18.11.1454. View

20.

Pomann J, Rudner E . Scleromyxedema revisited. Int J Dermatol. 2003; 42(1):31-5. DOI: 10.1046/j.1365-4362.2003.01565.x. View