Prostaglandin E₂ (PGE₂) in tissue regeneration: Its role and therapeutic strategies

Prostaglandin E₂ (PGE₂), which is traditionally recognized as a pro-inflammatory mediator target, is now recognized for its role in tissue regeneration. PGE₂ drives stem cell proliferation, M2 macrophage polarization, angiogenesis, and extracellular matrix (ECM) remodeling via E-type prostanoid (EP) receptor signaling, promoting repair in the skin, muscle, bone, heart, liver, kidney, and intestine. Despite these promising effects, the clinical translation of PGE₂ has been hindered by challenges such as a short half-life due to rapid degradation by 15-hydroxyprostaglandin dehydrogenase (15-PGDH), limited EP receptor subtype specificity, or oncogenic risks in certain contexts. This review explores the regenerative mechanisms of PGE₂, its tissue-specific roles, and innovative strategies to optimize therapeutic efficacy while minimizing adverse effects in regenerative medicine. See also the graphical abstract(Fig. 1).