A TGFΒ-responsive gene signature is associated with a subset of diffuse scleroderma with increased disease severity

Jennifer L. Sargent, Ausra Milano, Swati Bhattacharyya, John Varga, M. Kari Connolly, Howard Y. Chang, Michael L. Whitfield

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Systemic sclerosis is a complex disease with widespread skin fibrosis and variable visceral organ involvement. Since transforming growth factor-Β (TGFΒ) has been implicated in driving fibrosis in systemic sclerosis, a mechanism-derived gene expression signature was used to assay TGFΒ-responsive gene expression in the skin of patients with systemic sclerosis (SSc). Primary dermal fibroblasts from patients with diffuse SSc (dSSc) and healthy controls were treated with TGFΒ, and the genome-wide gene expression was measured on DNA microarrays over a time course of 24 hours. Eight hundred and ninety-four probes representing 674 uniquely annotated genes were identified as TGFΒ responsive. Expression of the TGFΒ-responsive signature was examined in skin biopsies from 17 dSSc, seven limited SSc (lSSc), three morphea patients, and six healthy controls. The TGFΒ-responsive signature was expressed in 10 out of 17 dSSc skin biopsies, but was not found in lSSc, morphea, or healthy control biopsies. Expression of dSSC the TGFΒ-responsive signature stratifies patients into two major groups, one of which corresponds to the diffuse-proliferation intrinsic subset that showed higher modified Rodnan skin score and a higher likelihood of scleroderma lung disease. The TGFΒ-responsive signature is found in only a subset of dSSc patients who could be targeted by specific therapies.

Original languageEnglish (US)
Pages (from-to)694-705
Number of pages12
JournalJournal of Investigative Dermatology
Volume130
Issue number3
DOIs
StatePublished - Mar 1 2010

Fingerprint

Diffuse Scleroderma
Transforming Growth Factors
Genes
Systemic Scleroderma
Skin
Biopsy
Gene expression
Localized Scleroderma
Fibrosis
Gene Expression
Pulmonary diseases
Fibroblasts
Microarrays
Oligonucleotide Array Sequence Analysis
Transcriptome
Lung Diseases
Assays
Genome
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Sargent, Jennifer L. ; Milano, Ausra ; Bhattacharyya, Swati ; Varga, John ; Connolly, M. Kari ; Chang, Howard Y. ; Whitfield, Michael L. / A TGFΒ-responsive gene signature is associated with a subset of diffuse scleroderma with increased disease severity. In: Journal of Investigative Dermatology. 2010 ; Vol. 130, No. 3. pp. 694-705.
@article{fe4a21a4a78149c690727850d3d2210d,
title = "A TGFΒ-responsive gene signature is associated with a subset of diffuse scleroderma with increased disease severity",
abstract = "Systemic sclerosis is a complex disease with widespread skin fibrosis and variable visceral organ involvement. Since transforming growth factor-Β (TGFΒ) has been implicated in driving fibrosis in systemic sclerosis, a mechanism-derived gene expression signature was used to assay TGFΒ-responsive gene expression in the skin of patients with systemic sclerosis (SSc). Primary dermal fibroblasts from patients with diffuse SSc (dSSc) and healthy controls were treated with TGFΒ, and the genome-wide gene expression was measured on DNA microarrays over a time course of 24 hours. Eight hundred and ninety-four probes representing 674 uniquely annotated genes were identified as TGFΒ responsive. Expression of the TGFΒ-responsive signature was examined in skin biopsies from 17 dSSc, seven limited SSc (lSSc), three morphea patients, and six healthy controls. The TGFΒ-responsive signature was expressed in 10 out of 17 dSSc skin biopsies, but was not found in lSSc, morphea, or healthy control biopsies. Expression of dSSC the TGFΒ-responsive signature stratifies patients into two major groups, one of which corresponds to the diffuse-proliferation intrinsic subset that showed higher modified Rodnan skin score and a higher likelihood of scleroderma lung disease. The TGFΒ-responsive signature is found in only a subset of dSSc patients who could be targeted by specific therapies.",
author = "Sargent, {Jennifer L.} and Ausra Milano and Swati Bhattacharyya and John Varga and Connolly, {M. Kari} and Chang, {Howard Y.} and Whitfield, {Michael L.}",
year = "2010",
month = "3",
day = "1",
doi = "10.1038/jid.2009.318",
language = "English (US)",
volume = "130",
pages = "694--705",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "3",

}

A TGFΒ-responsive gene signature is associated with a subset of diffuse scleroderma with increased disease severity. / Sargent, Jennifer L.; Milano, Ausra; Bhattacharyya, Swati; Varga, John; Connolly, M. Kari; Chang, Howard Y.; Whitfield, Michael L.

In: Journal of Investigative Dermatology, Vol. 130, No. 3, 01.03.2010, p. 694-705.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A TGFΒ-responsive gene signature is associated with a subset of diffuse scleroderma with increased disease severity

AU - Sargent, Jennifer L.

AU - Milano, Ausra

AU - Bhattacharyya, Swati

AU - Varga, John

AU - Connolly, M. Kari

AU - Chang, Howard Y.

AU - Whitfield, Michael L.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Systemic sclerosis is a complex disease with widespread skin fibrosis and variable visceral organ involvement. Since transforming growth factor-Β (TGFΒ) has been implicated in driving fibrosis in systemic sclerosis, a mechanism-derived gene expression signature was used to assay TGFΒ-responsive gene expression in the skin of patients with systemic sclerosis (SSc). Primary dermal fibroblasts from patients with diffuse SSc (dSSc) and healthy controls were treated with TGFΒ, and the genome-wide gene expression was measured on DNA microarrays over a time course of 24 hours. Eight hundred and ninety-four probes representing 674 uniquely annotated genes were identified as TGFΒ responsive. Expression of the TGFΒ-responsive signature was examined in skin biopsies from 17 dSSc, seven limited SSc (lSSc), three morphea patients, and six healthy controls. The TGFΒ-responsive signature was expressed in 10 out of 17 dSSc skin biopsies, but was not found in lSSc, morphea, or healthy control biopsies. Expression of dSSC the TGFΒ-responsive signature stratifies patients into two major groups, one of which corresponds to the diffuse-proliferation intrinsic subset that showed higher modified Rodnan skin score and a higher likelihood of scleroderma lung disease. The TGFΒ-responsive signature is found in only a subset of dSSc patients who could be targeted by specific therapies.

AB - Systemic sclerosis is a complex disease with widespread skin fibrosis and variable visceral organ involvement. Since transforming growth factor-Β (TGFΒ) has been implicated in driving fibrosis in systemic sclerosis, a mechanism-derived gene expression signature was used to assay TGFΒ-responsive gene expression in the skin of patients with systemic sclerosis (SSc). Primary dermal fibroblasts from patients with diffuse SSc (dSSc) and healthy controls were treated with TGFΒ, and the genome-wide gene expression was measured on DNA microarrays over a time course of 24 hours. Eight hundred and ninety-four probes representing 674 uniquely annotated genes were identified as TGFΒ responsive. Expression of the TGFΒ-responsive signature was examined in skin biopsies from 17 dSSc, seven limited SSc (lSSc), three morphea patients, and six healthy controls. The TGFΒ-responsive signature was expressed in 10 out of 17 dSSc skin biopsies, but was not found in lSSc, morphea, or healthy control biopsies. Expression of dSSC the TGFΒ-responsive signature stratifies patients into two major groups, one of which corresponds to the diffuse-proliferation intrinsic subset that showed higher modified Rodnan skin score and a higher likelihood of scleroderma lung disease. The TGFΒ-responsive signature is found in only a subset of dSSc patients who could be targeted by specific therapies.

UR - http://www.scopus.com/inward/record.url?scp=76649115304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76649115304&partnerID=8YFLogxK

U2 - 10.1038/jid.2009.318

DO - 10.1038/jid.2009.318

M3 - Article

C2 - 19812599

AN - SCOPUS:76649115304

VL - 130

SP - 694

EP - 705

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 3

ER -