The following is a summary of “Extracellular Matrix–Derived Damage-Associated Molecular Patterns (DAMP): Implications in Systemic Sclerosis and Fibrosis,” published in the October 2023 issue of Investigative Dermatology by Bale, et al.
Damage-associated molecular patterns, or DAMPs, are molecules inside cells that are released when cells are under stress or when tissue is injured over and over again. They bind to toll-like receptors (TLRs) naturally. These DAMPs are either actively released into the extracellular environment by immune cells or passively released into the extracellular environment by harmed cells. They are also made when mRNA versions of extracellular matrix (ECM) glycoproteins are spliced in different ways. DAMPs start natural immunity reactions when they are noticed by pattern recognition receptors (PRRs) like TLRs.
Along with TLRs, the best-studied PRRs are nucleotide-binding oligomerization domain–like receptors, RIG-I–like RNA helicases, C-type lectin receptors, and many more. Systemic sclerosis (SSc) is a long-term autoimmune disease that causes inflammation and scar tissue in many systems. By looking at a wide range of SSc-related DAMPs, the researchers found that tenascin C and fibronectin-containing extra domain A are the most highly increased ECM glycoproteins in SSc skin and lung samples.
These DAMPs turn on TLR4 on local stromal cells, which causes profibrotic reactions and long-term activation of myofibroblasts, which leads to progressive fibrosis. This review sums up what they know about the complicated roles that DAMPs play in the development and failure to resolve fibrosis in general, with a focus on SSc, and it also looks at possible treatment methods that target DAMPs.