Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4
| Autor: | Chia-Yang Liu, Atsushi Nambu, Yoshiro Suzuki, Winston Whei-Yang Kao, Masayasu Miyajima, Kenta Kobayashi, Makoto Tominaga, Takayoshi Sumioka, Kunitoshi Uchida, Hiromi Sano, Shizuya Saika, James V. Jester, Peter S. Reinach, Yuka Okada, Hiroki Iwanishi, Kumi Shirai, Syu-ichi Hirai, Kana Ichikawa |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
TRPV Cation Channels Biology Pathology and Forensic Medicine Gene Knockout Techniques Mice 03 medical and health sciences Trigeminal ganglion 0302 clinical medicine medicine Animals Trigeminal Nerve Progenitor cell Molecular Biology Cells Cultured Corneal epithelium Trigeminal nerve Wound Healing Stem Cells Epithelium Corneal Cell Biology eye diseases Epithelium Cell biology Ganglion 030104 developmental biology Nerve growth factor medicine.anatomical_structure 030220 oncology & carcinogenesis sense organs Sensory nerve |
| Zdroj: | Laboratory Investigation. 99:210-230 |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/s41374-018-0118-4 |
| Popis: | In order to understand the pathobiology of neurotrophic keratopathy, we established a mouse model by coagulating the first branch of the trigeminal nerve (V1 nerve). In our model, the sensory nerve in the central cornea disappeared and remaining fibers were sparse in the peripheral limbal region. Impaired corneal epithelial healing in the mouse model was associated with suppression of both cell proliferation and expression of stem cell markers in peripheral/limbal epithelium as well as a reduction of transient receptor potential vanilloid 4 (TRPV4) expression in tissue. TRPV4 gene knockout also suppressed epithelial repair in mouse cornea, although it did not seem to directly modulate migration of epithelium. In a co-culture experiment, TRPV4-introduced KO trigeminal ganglion upregulated nerve growth factor (NGF) in cultured corneal epithelial cells, but ganglion with a control vector did not. TRPV4 gene introduction into a damaged V1 nerve rescues the impairment of epithelial healing in association with partial recovery of the stem/progenitor cell markers and upregulation of cell proliferation and of NGF expression in the peripheral/limbal epithelium. Gene transfer of TRPV4 did not accelerate the regeneration of nerve fibers. Sensory nerve TRPV4 is critical to maintain stemness of peripheral/limbal basal cells, and is one of the major mechanisms of homeostasis maintenance of corneal epithelium. |
| Databáze: | OpenAIRE |
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