Dioleoylphosphatidylglycerol Accelerates Corneal Epithelial Wound Healing
| Autor: | Mitchell A. Watsky, Lawrence O. Olala, Rachana Patel, Xiaowen Lu, Amy Estes, David Bogorad, Wendy B. Bollag, Ding Xie, Vivek Choudhary, Haixia Qin |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Blotting Western Limbus Corneae Transfection Cornea 03 medical and health sciences Mice 0302 clinical medicine In vivo Cell Movement medicine Phospholipase D Sf9 Cells Animals Humans Immunoprecipitation phospholipase D2 phosphatidylglycerol Cells Cultured Corneal epithelium Cell Proliferation Mice Knockout Aquaporin 3 Wound Healing integumentary system business.industry Epithelium Corneal Phosphatidylglycerols In vitro Epithelium eye diseases Cell biology 030104 developmental biology medicine.anatomical_structure Microscopy Fluorescence 030220 oncology & carcinogenesis sense organs Signal transduction Wound healing business Signal Transduction |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 0146-0404 |
| Popis: | Purpose In contact with the external environment, the cornea can easily be injured. Although corneal wounds generally heal rapidly, the pain and increased risk of infection associated with a damaged cornea, as well as the impaired healing observed in some individuals, emphasize the need for novel treatments to accelerate corneal healing. We previously demonstrated in epidermal keratinocytes that the glycerol channel aquaporin-3 (AQP3) interacts with phospholipase D2 (PLD2) to produce the signaling phospholipid phosphatidylglycerol (PG), which has been shown to accelerate skin wound healing in vivo. We hypothesized that the same signaling pathway might be operational in corneal epithelial cells. Methods We used co-immunoprecipitation, immunohistochemistry, scratch wound healing assays in vitro, and corneal epithelial wound healing assays in vivo to determine the role of the AQP3/PLD2/PG signaling pathway in corneal epithelium. Results AQP3 was present in human corneas in situ, and AQP3 and PLD2 were co-immunoprecipitated from corneal epithelial cell lysates. The two proteins could also be co-immunoprecipitated from insect cells simultaneously infected with AQP3- and PLD2-expressing baculoviruses, suggesting a likely direct interaction. A particular PG, dioleoylphosphatidylglycerol (DOPG), enhanced scratch wound healing of a corneal epithelial monolayer in vitro. DOPG also accelerated corneal epithelial wound healing in vivo, both in wild-type mice and in a mouse model exhibiting impaired corneal wound healing (AQP3 knockout mice). Conclusions These results indicate the importance of the AQP3/PLD2/PG signaling pathway in corneal epithelial cells and suggest the possibility of developing DOPG as a pharmacologic therapy to enhance corneal wound healing in patients. |
| Databáze: | OpenAIRE |
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