Amphiregulin and Fibrosis: Existing Evidence and Future Directions

The fibrotic progression of diseases is characterized by excessive deposition of extracellular matrix (ECM) proteins leading to an alteration in tissue structure, often based on the activation of epithelial-to-mesenchymal transition (EMT). This determines decreased or completely impaired organ function, compromising quality of life and affecting vital organs. Fibrotic phenomena have recently been observed in autoimmune diseases and correlated with the activation of transduction cascades that trigger chronic inflammation. Currently, effective therapeutic options remain limited due to the numerous molecular mechanisms that are activated and intersect with each other. Amphiregulin (AREG), a ligand for the epidermal growth factor receptor (EGFR), is involved in physiological cellular processes, but emerging data suggest that it plays a key role as a protein located at the crossroads of various activation mechanisms. The critical role of AREG as a molecular bridge between inflammatory and fibrotic mechanisms has aroused our interest in deepening our understanding of AREG involvement in the fibrotic processes identified, to date, in inflammatory autoimmune diseases. The aim of this review is to evaluate emerging targeted interventions to modulate AREG-mediated molecular pathways in fibrotic processes observed in autoimmune diseases, starting with the structure of AREG and the molecular mechanisms in which the protein is involved.