Fibrotic diseases form excess scar tissue in organs and skin and contribute to a large share of deaths in developed nations. Researchers at Yale School of Medicine report two complementary discoveries that suggest new therapeutic approaches. One study, published in Blood, presents a human monoclonal antibody that targets epiregulin, a ligand for the epidermal growth factor receptor (EGFR). Earlier work had shown elevated epiregulin in scleroderma skin, so the team hypothesized that excess epiregulin overactivates EGFR and drives fibrosis.
The investigators compared single-cell RNA sequencing across patients with scleroderma and with fibrotic graft‑versus‑host disease and confirmed upregulated epiregulin as a common feature. They then tested the anti‑epiregulin antibody in humanized mouse models and in patient skin biopsies; inhibiting epiregulin reduced biomarkers linked to fibrosis, supporting its therapeutic potential.
A separate study in Nature Communications compared seven inflammatory skin diseases, including atopic dermatitis and psoriasis, with fibrotic conditions such as scleroderma, graft‑versus‑host disease and lupus. The analysis revealed greater STAT1 activity in fibroblasts from fibrotic diseases. Experiments using STAT1‑deficient mice and cultured fibroblasts showed that STAT1 is required for fibrotic gene activation and that EGFR can activate STAT1 independently of Janus kinases (JAKs). This finding helps explain why JAK inhibitors can work for some inflammatory skin conditions but are less effective against fibrosis.
Investigators note that inhibiting the epiregulin–EGFR pathway should be relatively safe because it is active mainly during injury or inflammation. The team plans to test the anti‑epiregulin therapy in other fibrotic diseases such as lupus and hidradenitis suppurativa. The studies point to two promising avenues: direct epiregulin inhibition and targeting the EGFR–STAT1 pathway.
Difficult words
- fibrosis — formation of excess scar tissue in organs
- epiregulin — a protein that binds and activates EGFR
- epidermal growth factor receptor — cell surface receptor activated by growth factors
- monoclonal antibody — a laboratory-made immune protein that binds one target
- single-cell RNA sequencing — method to measure gene activity in individual cells
- biomarker — measurable sign indicating a biological conditionbiomarkers
- inhibit — to reduce or block a biological activityinhibiting
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Discussion questions
- What could be the advantages and possible risks of blocking the epiregulin–EGFR pathway in patients? Give reasons from the article.
- How might these findings change treatment approaches for other fibrotic diseases such as lupus or hidradenitis suppurativa? Describe possible benefits and challenges.
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