Related Experiment Video
Updated: Jul 23, 2025
10:21
Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
Published on: June 14, 2016
10.1K
Extracellular Matrix-Derived Damage-Associated Molecular Patterns (DAMP): Implications in Systemic Sclerosis and
Swarna Bale1, Priyanka Verma1, John Varga1
1Michigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
The Journal of Investigative Dermatology
|July 15, 2023
Summary
Damage-associated molecular patterns (DAMPs) activate toll-like receptors (TLRs), driving fibrosis in systemic sclerosis (SSc). Targeting these DAMPs offers potential new therapies for fibrotic diseases.
Area of Science:
- Immunology
- Fibrosis Research
- Autoimmune Diseases
Background:
- Damage-associated molecular patterns (DAMPs) are endogenous molecules released during cellular stress or injury.
- Pattern recognition receptors (PRRs), including toll-like receptors (TLRs), recognize DAMPs, initiating innate immune responses.
- Systemic sclerosis (SSc) is a fibrotic autoimmune disease with significant inflammation.
Purpose of the Study:
- To identify DAMPs associated with systemic sclerosis (SSc).
- To investigate the role of identified DAMPs in SSc pathogenesis.
- To explore therapeutic strategies targeting DAMPs in fibrosis.
Main Methods:
- Unbiased survey of DAMPs in SSc skin and lung biopsies.
- Analysis of DAMPs activating TLR4 on stromal cells.
- Review of DAMP functions in fibrosis and SSc.
Main Results:
- Fibronectin-containing extra domain A and tenascin C were identified as highly upregulated DAMPs in SSc.
- These DAMPs activate TLR4, promoting profibrotic responses and myofibroblast activation.
- Sustained activation leads to progressive fibrosis in SSc.
Conclusions:
- Specific DAMPs contribute significantly to SSc progression.
- Targeting DAMP-TLR4 interactions may offer therapeutic benefits for SSc.
- Understanding DAMPs is crucial for managing fibrotic diseases.
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