A moderate dosage of prostaglandin E2-mediated annexin A1 upregulation promotes alkali-burned corneal repair

Corneal alkali burn remains a clinical challenge in ocular emergency, necessitating the development of effective therapeutic drugs. Here, we observed the arachidonic acid metabolic disorders of corneas induced by alkali burns and aimed to explore the role of Prostaglandin E2 (PGE2), a critical metabolite of arachidonic acid, in the repair of alkali-burned corneas. We found a moderate dosage of PGE2 promoted the alkali-burned corneal epithelial repair, whereas a high dosage of PGE2 exhibited a contrary effect. This divergent effect is attributed to different dosages of PGE2 regulating ANXA1 expression differently. Mechanically, a high dosage of PGE2 induced higher GATA3 expression, followed by enhanced GATA3 binding to the ANXA1 promoter to inhibit ANXA1 expression. In contrast, a moderate dosage of PGE2 increased CREB1 phosphorylation and reduced GATA3 binding to the ANXA1 promoter, promoting ANXA1 expression. We believe PGE2 and its regulatory target ANXA1 could be potential drugs for alkali-burned corneas. [Display omitted] •A moderate dosage of PGE2 increases ANXA1 to accelerate alkali-burned corneal repair•A high dosage of PGE2 reduces ANXA1 to postpone alkali-burned corneal repair•A high dosage of PGE2 downregulates ANXA1 by enhancing GATA3 binding to its promoter•A moderate dosage of PGE2 induces higher GATA3 and lower CREB1 phosphorylation Medicine; Pharmaceutical science; Pharmacy; Physiology; Molecular biology