Substance P promotes diabetic corneal epithelial wound healing through molecular mechanisms mediated via the neurokinin-1 receptor
- Lingling Yang1,#,
- Guohu Di1,#,
- Xia Qi1,
- Mingli Qu1,
- Yao Wang1,
- Haoyun Duan1,
- Patrik Danielson2,
- Lixin Xie1,* and
- Qingjun Zhou1,*
- 1State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
- 2Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden
- *Corresponding Author: Qingjun Zhou & Lixin Xie, Email: ;
# Contribute equally to this study
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 with attenuated corneal sensation, mitochondrial dysfunction, and impairments of Akt-, EGFR-, and Sirt1-activation, as well as decreased reactive oxygen species (ROS) scavenging capacity. However, SP application promoted the epithelial wound healing, the recovery of corneal sensation, the improvement of mitochondrial function, and the 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 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 recssssseptor 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.
- Received January 29, 2014.
- Accepted June 23, 2014.
- © 2014 by the American Diabetes Association.
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