2. Academic Validation
  3. Insulin Promotes Corneal Nerve Repair and Wound Healing in Type 1 Diabetic Mice by Enhancing Wnt/β-Catenin Signaling

Insulin Promotes Corneal Nerve Repair and Wound Healing in Type 1 Diabetic Mice by Enhancing Wnt/β-Catenin Signaling

  • Am J Pathol. 2020 Nov;190(11):2237-2250. doi: 10.1016/j.ajpath.2020.08.006.
Shuo Yang 1,  Yangyang Zhang 2,  Zhaohua Zhang 2,  Jing Dan 2,  Qingjun Zhou 2,  Xiaochuan Wang 2,  Weina Li 2,  Li Zhou 2,  Lingling Yang 3,  Lixin Xie 4
Affiliations

Affiliations

  • 1 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, China; Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan, China.
  • 2 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, China.
  • 3 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, China. Electronic address: lingling6008@126.com.
  • 4 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, China. Electronic address: lxxie@sdfmu.edu.cn.
PMID: 32858016 DOI: 10.1016/j.ajpath.2020.08.006
Abstract

The Insulin and Wnt signaling pathways are involved in cell proliferation, tissue homeostasis, and tumorigenesis. However, their interrelationship in the pathophysiological process of diabetic corneal injury remains unclear. In this study, the role of Insulin in the diabetic cornea was investigated in vitro, using cultured TKE2 cells and trigeminal ganglion neurons, and in vivo, by assessing corneal wound-healing responses in diabetic mice. A selective Wnt antagonist (XAV-939) and activator (BML-284) were used to regulate the interactions between Insulin and the Wnt pathway. The results demonstrated that Insulin promoted corneal epithelial wound healing and sensation recovery, whereas the expression of molecules involved in the Wnt/β-catenin pathway was also up-regulated in the injured corneal epithelium. However, XAV-939 limited the insulin-induced epithelial and corneal nerve repair. By contrast, BML-284 treatment promoted the healing of the corneal epithelium and corneal nerve repair in diabetic mice. These results indicate that Insulin, via Wnt signaling, contributes to diabetic corneal epithelial wound healing and nerve injury recovery and is, therefore, a potential protective factor for diabetic corneal epithelial wounds and nerve injury.

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