title: Ciliary neurotrophic factor promotes the activation of corneal epithelial stem/progenitor cells and accelerates corneal epithelial wound healing.
abstract: Ciliary neurotrophic factor (CNTF), a well-known neuroprotective cytokine, has been found to play an important role in neurogenesis and functional regulations of neural stem cells. As one of the most innervated tissue, however, the role of CNTF in cornea epithelium remains unclear. This study was to explore the roles and mechanisms of CNTF in the activation of corneal epithelial stem/progenitor cells and wound healing of both normal and diabetic mouse corneal epithelium. In mice subjecting to mechanical removal of corneal epithelium, the corneal epithelial stem/progenitor cell activation and wound healing were promoted by exogenous CNTF application, while delayed by CNTF neutralizing antibody. In cultured corneal epithelial stem/progenitor cells, CNTF enhanced the colony-forming efficiency, stimulated the mitogenic proliferation, and upregulated the expression levels of corneal epithelial stem/progenitor cell-associated transcription factors. Furthermore, the promotion of CNTF on the corneal epithelial stem/progenitor cell activation and wound healing was mediated by the activation of STAT3. Moreover, in diabetic mice, the content of CNTF in corneal epithelium decreased significantly when compared with that of normal mice, and the supplement of CNTF promoted the diabetic corneal epithelial wound healing, accompanied with the advanced activation of corneal epithelial stem/progenitor cells and the regeneration of corneal nerve fibers. Thus, the capability of expanding corneal epithelial stem/progenitor cells and promoting corneal epithelial wound healing and nerve regeneration indicates the potential application of CNTF in ameliorating limbal stem cell deficiency and treating diabetic keratopathy.
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, People's Republic of China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Guohu
authors.initials: G
authors.lastname: Di
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Qi
authors.forename: Haoyun
authors.initials: H
authors.lastname: Duan
authors.forename: Lixin
authors.initials: L
authors.lastname: Xie
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D019573:Epithelium, Corneal / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D020934:Ciliary Neurotrophic Factor; D050796:STAT3 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt
keywords: Ciliary neurotrophic factor; Corneal epithelial stem/progenitor cells; Diabetes; Nerve regeneration; Wound healing