Protective effects of pituitary adenylate cyclase-activating peptide (PACAP) on high glucose-induced damage in human corneal epithelial cell
Abstract Background Diabetic 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 whethe...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
|
| Series: | BMC Ophthalmology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12886-025-04309-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849345177654657024 |
|---|---|
| author | Yanan Bao Bing Li |
| author_facet | Yanan Bao Bing Li |
| author_sort | Yanan Bao |
| collection | DOAJ |
| description | Abstract Background Diabetic 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. Methods HCECs 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. Results Compared 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. Conclusions Our 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. |
| format | Article |
| id | doaj-art-fabdf28ec30a4d21a8e02ed23a07ddf9 |
| institution | Kabale University |
| issn | 1471-2415 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Ophthalmology |
| spelling | doaj-art-fabdf28ec30a4d21a8e02ed23a07ddf92025-08-20T03:42:30ZengBMCBMC Ophthalmology1471-24152025-08-0125111110.1186/s12886-025-04309-zProtective effects of pituitary adenylate cyclase-activating peptide (PACAP) on high glucose-induced damage in human corneal epithelial cellYanan Bao0Bing Li1Department of Ophthalmology, First Affiliated Hospital of Jinzhou Medical UniversityDepartment of Ophthalmology, First Affiliated Hospital of Jinzhou Medical UniversityAbstract Background Diabetic 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. Methods HCECs 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. Results Compared 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. Conclusions Our 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.https://doi.org/10.1186/s12886-025-04309-zPeptides activated by pituitary adenylate cyclaseHuman corneal epithelial cellsHigh glucoseDiabetic keratopathyDiabetic complications. |
| spellingShingle | Yanan Bao Bing Li Protective effects of pituitary adenylate cyclase-activating peptide (PACAP) on high glucose-induced damage in human corneal epithelial cell BMC Ophthalmology Peptides activated by pituitary adenylate cyclase Human corneal epithelial cells High glucose Diabetic keratopathy Diabetic complications. |
| title | Protective effects of pituitary adenylate cyclase-activating peptide (PACAP) on high glucose-induced damage in human corneal epithelial cell |
| title_full | Protective effects of pituitary adenylate cyclase-activating peptide (PACAP) on high glucose-induced damage in human corneal epithelial cell |
| title_fullStr | Protective effects of pituitary adenylate cyclase-activating peptide (PACAP) on high glucose-induced damage in human corneal epithelial cell |
| title_full_unstemmed | Protective effects of pituitary adenylate cyclase-activating peptide (PACAP) on high glucose-induced damage in human corneal epithelial cell |
| title_short | Protective effects of pituitary adenylate cyclase-activating peptide (PACAP) on high glucose-induced damage in human corneal epithelial cell |
| title_sort | protective effects of pituitary adenylate cyclase activating peptide pacap on high glucose induced damage in human corneal epithelial cell |
| topic | Peptides activated by pituitary adenylate cyclase Human corneal epithelial cells High glucose Diabetic keratopathy Diabetic complications. |
| url | https://doi.org/10.1186/s12886-025-04309-z |
| work_keys_str_mv | AT yananbao protectiveeffectsofpituitaryadenylatecyclaseactivatingpeptidepacaponhighglucoseinduceddamageinhumancornealepithelialcell AT bingli protectiveeffectsofpituitaryadenylatecyclaseactivatingpeptidepacaponhighglucoseinduceddamageinhumancornealepithelialcell |