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Netrin-1 promotes diabetic corneal wound healing through molecular mechanisms mediated via the adenosine 2B receptor.
- Source :
-
Scientific reports [Sci Rep] 2018 Apr 16; Vol. 8 (1), pp. 5994. Date of Electronic Publication: 2018 Apr 16. - Publication Year :
- 2018
-
Abstract
- Netrins are secreted chemoattractants with the roles in axon guidance, cell migration and epithelial plasticity. In the present study, we investigated the roles of netrin-1 in the regulation of corneal epithelial wound healing, inflammation response and nerve fiber regeneration in diabetic mice and cultured corneal epithelial cells. In diabetic mice, the expression of netrin-1 was decreased when compared with that of normal mice. Furthermore, high glucose blocked the wounding-induced up-regulation of netrin-1 expression in corneal epithelial cells. Exogenous netrin-1 promoted the corneal epithelial wound healing in diabetic mice, and facilitated the proliferation and migration by reactivating the phosphorylation of ERK and EGFR in high-glucose treated corneal epithelial cells. Moreover, netrin-1 decreased the neutrophil infiltration and promoted M2 macrophage transition, accompanied with the attenuated expression of pro-inflammatory factors in diabetic mouse corneal epithelium. The promotions of netrin-1 on corneal epithelial wound healing and inflammation resolution were mediated at least through the adenosine 2B receptor. In addition, netrin-1 promoted the regeneration of corneal nerve fibers that was impaired in diabetic mice. Taken together, netrin-1 regulates corneal epithelial wound healing, inflammation response and nerve fiber regeneration in diabetic mice, indicating the potential application for the therapy of diabetic keratopathy.
- Subjects :
- Animals
Cell Movement
Cornea metabolism
Cornea pathology
Corneal Diseases metabolism
Corneal Diseases pathology
Diabetes Mellitus, Experimental metabolism
Diabetes Mellitus, Experimental pathology
Hyperglycemia metabolism
Hyperglycemia pathology
Inflammation etiology
Inflammation metabolism
Inflammation pathology
Male
Mice, Inbred C57BL
Netrin-1 analysis
Receptor, Adenosine A2B analysis
Corneal Diseases etiology
Diabetes Mellitus, Experimental complications
Hyperglycemia complications
Netrin-1 metabolism
Receptor, Adenosine A2B metabolism
Wound Healing
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 29662125
- Full Text :
- https://doi.org/10.1038/s41598-018-24506-9