Cited by 197Systemic Sclerosis and Related DiseasesDupuytren's Contracture and TreatmentsConnective tissue disorders research

Scleroderma pathogenesis: a pivotal role for fibroblasts as effector cells

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Gilbane, Adrian J, Denton, Christopher P, Holmes, Alan M·2013·Arthritis Research & Therapy

Abstract

Scleroderma (systemic sclerosis; SSc) is characterised by fibrosis of the skin and internal organs in the context of autoimmunity and vascular perturbation. Overproduction of extracellular matrix components and loss of specialised epithelial structures are analogous to the process of scar formation after tissue injury. Fibroblasts are the resident cells of connective tissue that become activated at sites of damage and are likely to be important effector cells in SSc. Differentiation into myofibroblasts is a hallmark process, although the mechanisms and cellular origins of this important fibroblastic cell are still unclear. This article reviews fibroblast biology in the context of SSc and highlights the potentially important place of fibroblast effector cells in fibrosis. Moreover, the heterogeneity of fibroblast properties, multiplicity of regulatory pathways and diversity of origin for myofibroblasts may underpin clinical diversity in SSc, and provide novel avenues for targeted therapy.

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  • Organs such as kidney, intestine and myocard can also be affected by myofibroblast-driven fibrosis in SSc.

    “In addtion, organs such as kidney, intestine and myocard can also be affected by myofibroblast-driven fibrosis in SSc (18).”

    From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [18]

  • Myofibroblasts have long been associated with SSc pathophysiology.

    “Myofibroblasts have long been associated with SSc pathophysiology (18).”

    From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [18]

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Research works printed but not linked: 1

  1. Sonnylal S Denton CP Zheng B Keene DR He R Adams HP Vanpelt CS Geng YJ Deng JM Behringer RR de Crombrugghe B Postnatal induction of transforming growth factor beta signaling in fibroblasts of mice recapitulates clinical, histologic, and biochemical features of scleroderma Arthritis Rheum 2007 15 334 344 10.1002/art.22328 17195237 · DOI

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Authors
Gilbane, A. J., Denton, C. P., & Holmes, A. M.
Affiliations
The Royal Free Hospital (GB)
Corresponding author
Denton, Christopher P
Venue
Arthritis Research & Therapy
Published
2013
Volume
15
Issue
3
Pages
215
ISSN
1478-6354 (ISSN-L)
OpenAlex
W2147084913
Cited by
196
References
64
Citations by year
2026: 12 · 2025: 8 · 2024: 14 · 2023: 14 · 2022: 18 · 2021: 21 · 2020: 14 · 2019: 17 · 2018: 17 · 2017: 17 · 2016: 15 · 2015: 14 · 2014: 12 · 2013: 1
FWCI
2.06
Type
journal article
Language
en
Open access
Locations
  • Arthritis Research & Therapy (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Versus Arthritis (19920)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
  • Health Sciences › Medicine › Rheumatology › Dupuytren's Contracture and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
Keywords
systemic sclerosis, fibroblasts, myofibroblasts, fibrosis, extracellular matrix, autoimmunity, fibroblast heterogeneity, fibroblast origin, targeted therapy
MeSH terms
Extracellular Matrix, Fibroblasts, Humans, Scleroderma, Systemic

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