Fibrosis in systemic sclerosis: Common and unique pathobiology

Swati Bhattacharyya, Jun Wei, Warren G. Tourtellotte, Monique Hinchcliff, Cara G. Gottardi, John Varga*

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Fibrosis in systemic sclerosis (SSc), a complex polygenic disease associated with autoimmunity and proliferative/obliterative vasculopathy, shares pathobiologic features in common with other fibrosing illnesses, but also has distinguishing characteristics. Fibroblast activation induced by transforming growth factor-β (TGF-β), Wnts and innate immune receptors, along with oxidative stress and reactive oxygen species (ROS) are implicated in pathogenesis. On the other hand, the roles of endothelial-mesenchymal differentiation and bone marrow-derived fibrocytes remain to be established. Fibrotic responses are modulated by transcriptional activators and cofactors, epigenetic factors, and microRNAs that can amplify or inhibit ligand-induced signaling. The nuclear orphan receptor PPAR-γ appears to be important in governing the duration and intensity of fibroblast activation and mesenchymal progenitor cell differentiation, and defects in PPAR-γ expression or function in SSc may underlie the uncontrolled progression of fibrosis. Identifying the perturbations in signaling pathways and cellular differentiation programs responsible for tissue damage and fibrosis in SSc allows their selective targeting using novel compounds, or by innovative uses of already-approved drugs (drug repurposing).

Original languageEnglish (US)
Article numberS18
JournalFibrogenesis and Tissue Repair
Volume5
Issue numberSUPPL.1
DOIs
StatePublished - Jun 6 2012

Fingerprint

Systemic Scleroderma
Peroxisome Proliferator-Activated Receptors
Fibrosis
Drug Repositioning
Fibroblasts
Orphan Nuclear Receptors
Transforming Growth Factors
MicroRNAs
Autoimmunity
Mesenchymal Stromal Cells
Epigenomics
Cell Differentiation
Reactive Oxygen Species
Oxidative Stress
Bone Marrow
Ligands
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Rheumatology
  • Hepatology
  • Dermatology
  • Gastroenterology

Cite this

Bhattacharyya, Swati ; Wei, Jun ; Tourtellotte, Warren G. ; Hinchcliff, Monique ; Gottardi, Cara G. ; Varga, John. / Fibrosis in systemic sclerosis : Common and unique pathobiology. In: Fibrogenesis and Tissue Repair. 2012 ; Vol. 5, No. SUPPL.1.
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Fibrosis in systemic sclerosis : Common and unique pathobiology. / Bhattacharyya, Swati; Wei, Jun; Tourtellotte, Warren G.; Hinchcliff, Monique; Gottardi, Cara G.; Varga, John.

In: Fibrogenesis and Tissue Repair, Vol. 5, No. SUPPL.1, S18, 06.06.2012.

Research output: Contribution to journalArticle

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