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Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor
Abstract
Substance P (SP) is a neuropeptide, predominantly released from sensory nerve fibers, with a potentially protective role in diabetic corneal epithelial wound healing. However, the molecular mechanism remains unclear. We investigated the protective mechanism of SP against hyperglycemia-induced corneal epithelial wound healing defects, using type 1 diabetic mice and high glucose–treated corneal epithelial cells. Hyperglycemia induced delayed corneal epithelial wound healing, accompanied by attenuated corneal sensation, mitochondrial dysfunction, and impairments of Akt, epidermal growth factor receptor (EGFR), and Sirt1 activation, as well as decreased reactive oxygen species (ROS) scavenging capacity. However, SP application promoted epithelial wound healing, recovery of corneal sensation, improvement of mitochondrial function, and reactivation of Akt, EGFR, and Sirt1, as well as increased ROS scavenging capacity, in both diabetic mouse corneal epithelium and high glucose–treated corneal epithelial cells. The promotion of SP on diabetic corneal epithelial healing was completely abolished by a neurokinin-1 (NK-1) receptor antagonist. Moreover, the subconjunctival injection of NK-1 receptor antagonist also caused diabetic corneal pathological changes in normal mice. In conclusion, the results suggest that SP-NK-1 receptor signaling plays a critical role in the maintenance of corneal epithelium homeostasis, and that SP signaling through the NK-1 receptor contributes to the promotion of diabetic corneal epithelial wound healing by rescued activation of Akt, EGFR, and Sirt1, improvement of mitochondrial function, and increased ROS scavenging capacity.
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“SP accelerates the normal acute and chronic wound healing processes54–56.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [56]
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Self-citationSubstance P and thiorphan synergically enhance angiogenesis in wound healing
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Self-Retained Cryopreserved Amniotic Membrane for the Management of Corneal Ulcers
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Metadata
- Authors
- Yang, L., Di, G., Qi, X., Qu, M., Wang, Y., Duan, H., Danielson, P., Xie, L., & Zhou, Q.
- Affiliations
- Shandong First Medical University (CN)
- Umeå University (SE)
- Corresponding author
- Xie, Lixin
- Zhou, Qingjun
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2014-11-13
- Volume
- 63
- Issue
- 12
- Pages
- 4262-4274
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2158147611
- Cited by
- 184
- References
- 51
- Citations by year
- 2026: 4 · 2025: 21 · 2024: 17 · 2023: 17 · 2022: 15 · 2021: 18 · 2020: 28 · 2019: 19 · 2018: 13 · 2017: 12 · 2016: 12 · 2015: 8
- FWCI
- 8.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Corneal Surgery and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Surface and Contact Lens
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- substance P, neurokinin-1 receptor, corneal wound healing, hyperglycemia, type 1 diabetes, corneal sensitivity, mitochondrial dysfunction, Akt signaling, epidermal growth factor receptor, SIRT1, reactive oxygen species scavenging, neuropeptides
- MeSH terms
- Animals, Cell Line, Cornea, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Epithelial Cells, Hyperglycemia, Male, Mice, Inbred C57BL, Mitochondria, Substance P, Touch, Wound Healing, Reactive Oxygen Species, Receptors, Neurokinin-1, Neurotransmitter Agents, Proto-Oncogene Proteins c-akt, Mice, Sirtuin 1, Corneal Injuries, ErbB Receptors
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