Protective effect of pituitary adenylate cyclase activating polypeptide in diabetic keratopathy.

Autor: Maugeri G; Section of Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy., D'Amico AG; Section of System Biology, Department of Drug and Health Sciences, University of Catania, 95123 Catania, Italy., Magrì B; Section of Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy., Giunta S; Section of Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy., Saccone S; Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, 95123 Catania, Italy., Federico C; Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, 95123 Catania, Italy., Bucolo C; Pharmacology Section, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy., Musumeci G; Section of Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy., D'Agata V; Section of Anatomy, Histology and Movement Sciences, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy. Electronic address: vdagata@unict.it.
Jazyk: angličtina
Zdroj: Peptides [Peptides] 2023 Dec; Vol. 170, pp. 171107. Date of Electronic Publication: 2023 Sep 28.
DOI: 10.1016/j.peptides.2023.171107
Abstrakt: Diabetic keratopathy (DK) is the major complication of the cornea characterizing diabetes-affected patients. This ocular pathology is correlated with the hyperglycemic state leading to delayed corneal wound healing and recurrent corneal ulcers. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with widespread distribution throughout the body, and exerting cytoprotective effects in the neural and non-neuronal parts of the eye, including the cornea. The purpose of the present study was to investigate whether changes in PACAP expression can concur for delayed epithelial wound healing in diabetic cornea and whether the protective effect of the peptide could be mediated through the activation of the EGFR signaling pathway, which has been reported to be impaired in DK. Expression and distribution of PACAP, PAC1R, and EGFR were investigated through immunohistochemistry analysis in the cornea of normal and diabetic rats. The role of the peptide on wound healing during DK was evaluated in an in vitro model represented by rabbit corneal epithelial cells grown in high glucose conditions. Western blotting and immunofluorescence analysis were used to examine the ability of PACAP to induce the activation of the EGFR/ERK1/2 signaling pathway. Our results showed that in diabetic cornea the expression of PACAP, PAC1R, and EGFR is drastically reduced. The treatment with PACAP via PAC1R activation enhanced cell viability and corneal epithelium wound healing in cells grown under high glucose conditions. Furthermore, both EGFR and ERK1/2 signaling was induced upon the peptide treatment. Overall, our results showed the trophic efficiency of PACAP for enhancing the corneal epithelium re-epithelialization suggesting that the peptide could be beneficially valuable as a treatment for DK.
Competing Interests: Conflict of Interest The authors declare that there are no conflicts of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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