Protective effects of pituitary adenylate cyclase-activating peptide (PACAP) on high glucose-induced damage in human corneal epithelial cell.

backgroundDiabetic keratopathy (DK), a vision-threatening complication of diabetes mellitus, remains a significant clinical challenge. Pituitaries adenylate cyclase-activating peptide 38 (PACAP38) has been demonstrated to have neuroprotective effects. This study aimed to investigate whether PACAP38 mitigates high glucose (HG)-induced damage in human corneal epithelial cells (HCECs) and to elucidate the underlying mechanisms.

methodsHCECs were exposed to HG to simulate diabetic injury. Cell viability, apoptosis, migration, and autophagy were evaluated using Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell assays, and Western blotting, respectively.

resultsCompared to the normal control (NC) group, HG significantly suppressed cell proliferation (p < 0.01), whereas PACAP38 treatment restored proliferative capacity (p < 0.01). PACAP38 enhanced cell migration, counteracting HG-induced impairment. At the molecular level, HG downregulated Ki-67 and Bcl-2 mRNA expression, while PACAP38 markedly upregulated these markers (p < 0.01). Notably, the HG impaired the autophagy in HCEC cells, while the PACAP38 significantly increased the autophagic ability. Mechanistically, PACAP38 increased the expression of p-AMPK, p-ERK, and Bcl-2 while reducing p62 (p < 0.01). Crucially, these protective effects were abolished by the autophagy inhibitor 3-MA or the AMPK inhibitor compound C (p < 0.05), confirming pathway dependency.

conclusionsOur findings demonstrate that HG compromises HCEC proliferation and migration while promoting apoptosis. PACAP38 counteracts these detrimental effects by activating AMPK/ERK signaling, thereby enhancing cell survival and autophagy under hyperglycemic conditions. These results highlight PACAP38 as a promising therapeutic candidate for diabetic keratopathy.