Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 17, 2025 2 hours, 9 minutes ago
Thailand Medical News: Amphiregulin – The Overlooked Protein Fueling Dangerous Fibrosis in Autoimmune Diseases
Fibrosis – the gradual scarring and hardening of organs – is a serious outcome of many chronic autoimmune diseases. Once tissue is overtaken by excessive collagen and extracellular matrix deposits, organ function steadily declines, sometimes to the point of failure. Researchers from the Department of Translational Biomedicine and Neuroscience (DiBraiN), Section of Human Anatomy and Histology at the University of Bari “Aldo Moro” in Italy have uncovered how a little-known protein called amphiregulin (AREG) could be at the heart of this destructive process.
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Schematic representation of the most common AREG signalling pathways. AREG is produced as an immature protein (pro-AREG), which is cleaved by the matrix metalloproteinase, ADAM-17. The soluble mature AREG is released into the microenvironment, in which it activates EGFR via autocrine and paracrine signalling. AREG-mediated EGFR signalling stimulates the MAPK/ERK pathway, promoting fibroblast differentiation, ECM accumulation, and fibrotic disorders. AREG can interact through EGFR-independent mechanisms, with αvβ integrins activating TGF-β, which triggers EMT, leading to the development of fibrotic disease. ADAM-17 (A disintegrin and metalloprotease-17); BTC (betacellulin); ECM (extracellular matrix); EGFR (epidermal growth factor receptor); EGF (epidermal growth factor); EMT (epithelial–mesenchymal transition); ERK (extracellular signal-regulated kinase); HB-EGF (heparin-binding EGF-like growth factor); MAPK (mitogen-activated protein kinase); TGF-β (transforming growth factor-β).
AREG – The Molecular Bridge Between Inflammation and Scarring
This
Thailand Medical News report explores the findings showing that AREG, a member of the epidermal growth factor family, acts as a signal “switchboard” between chronic inflammation and fibrosis. Under normal conditions, AREG helps repair tissues after injury. But in autoimmune diseases, its signalling goes into overdrive. It binds to the epidermal growth factor receptor (EGFR), triggering powerful cascades – including PI3K/Akt and MAPK pathways – that cause fibroblasts to multiply and transform into myofibroblasts. These cells churn out collagen and fibronectin, leading to the scarring that gradually suffocates organs.
Evidence Across Multiple Organs and Diseases
Studies cited in the review reveal AREG’s elevated presence in fibrotic lungs, kidneys, liver, intestines, and heart tissue. In idiopathic pulmonary fibrosis (IPF), blocking AREG sharply reduces collagen build-up and preserves lung function in experimental models. In Crohn’s disease, high AREG levels in fibrotic intestinal tissue correlate with worse outcomes, and silencing the AREG gene reverses the damage in animal tests. In kidney disease, a novel Self-Assembled Micelle inhibitory RNA (SAMiRNA) targeting AREG reduced scarring and inflammation without the toxic effects seen with older therapies.
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strong>The Double-Edged Role of AREG
Interestingly, AREG’s effects are not always harmful. In some contexts, such as acute injury, it aids healing. But in chronic autoimmune diseases like systemic lupus erythematosus (SLE), Sjögren’s disease, and IPF, AREG appears to shift from being a repair agent to a fibrosis promoter. This role-switch seems linked to the type of immune cell producing AREG – macrophages, regulatory T cells, or fibroblasts – and the inflammatory environment.
Emerging Therapies Targeting AREG
Potential treatments are now focusing on shutting down AREG’s damaging effects while preserving its healing abilities. SAMiRNA technology has shown particular promise, as has the development of neutralizing antibodies that block AREG without directly interfering with EGFR – a strategy that could avoid the severe side effects of current EGFR inhibitors.
Why This Matters
The discovery of AREG’s pivotal role could change how doctors predict and treat fibrosis in autoimmune disease. Measuring AREG levels in blood or tissue might one day become a standard way to gauge disease severity and guide therapy choices. More importantly, targeted AREG-blocking drugs could slow or even halt the scarring process before organs suffer irreversible damage.
These findings highlight an urgent need for clinical trials to confirm the safety and effectiveness of anti-AREG approaches in humans. If successful, they could open the door to a new generation of precision therapies for conditions once considered untreatable.
The study findings were published in the peer reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/26/16/7678
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Read Also:
https://www.thailandmedical.news/news/long-covid-may-trigger-lasting-kidney-damage-due-to-persistent-inflammation-and-fibrosis
https://www.thailandmedical.news/news/covid-19-is-not-mild-as-most-will-develop-lung-fibrosis-10-percent-of-all-lung-transplants-in-u-s-now-go-to-post-covid-patients
https://www.thailandmedical.news/news/the-uniqueness-of-post-covid-lung-fibrosis-the-increased-expression-of-atp12a-protein
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