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

Hongling Liu; Xue Zhang; Qiang Tan; Lingling Ge; Jia Lu; Chunge Ren; Baishijiao Bian; Yijian Li; Yong Liu

doi:10.1016/j.isci.2023.108565

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

iScience. 2023 Nov 23;26(12):108565. doi: 10.1016/j.isci.2023.108565. eCollection 2023 Dec 15.

Authors

Hongling Liu^{1

2}, Xue Zhang^{1

2}, Qiang Tan^{1

2}, Lingling Ge^{1

2}, Jia Lu^{1

2}, Chunge Ren^{1

2}, Baishijiao Bian^{1

2

3

4}, Yijian Li^{1

2}, Yong Liu^{1

2

5}

Affiliations

¹ Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
² Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing 400038, China.
³ Army 953 Hospital, Shigatse Branch of Xinqiao Hospital, Third Military Medical University (Army Medical University), Shigatse 857000, China.
⁴ State Key Laboratory of Trauma, Burns, and Combined Injury, Department of Trauma Medical Center, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing 400042, China.
⁵ Jinfeng Laboratory, Chongqing 401329, China.

Abstract

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.

Keywords: Medicine; Molecular biology; Pharmaceutical science; Pharmacy; Physiology.