dEREGulated pathways: unraveling the role of epiregulin in skin, kidney, and lung fibrosis.

Abstract

The epidermal growth factor receptor (EGFR) signaling pathway is an evolutionary conserved mechanism to control cell behavior during tissue development and homeostasis. Deregulation of this pathway has been associated with abnormal cell behavior, including hyperproliferation, senescence, and an inflammatory cell phenotype, thereby contributing to pathologies across a variety of organs, including the kidneys, skin, and lungs. To date, there are seven distinct EGFR ligands described. Although binding of these ligands to the receptor is cell type-specific and spatio-temporally controlled with distinct affinities and kinetics, epiregulin (EREG) stands out as a long-acting EGFR ligand that emerges under pathological conditions, particularly in tissue fibrosis. Although EREG has been extensively studied in cancer, its contribution to the maladaptive remodeling of tissue is elusive. The aim of this review is to highlight the role of EREG in skin, kidney, and lung fibrosis and to discuss opportunities for therapeutic intervention.