title: Ascorbic Acid Promotes the Stemness of Corneal Epithelial Stem/Progenitor Cells and Accelerates Epithelial Wound Healing in the Cornea.
abstract: High concentration of ascorbic acid (vitamin C) has been found in corneal epithelium of various species. However, the specific functions and mechanisms of ascorbic acid in the repair of corneal epithelium are not clear. In this study, it was found that ascorbic acid accelerates corneal epithelial wound healing in vivo in mouse. In addition, ascorbic acid enhanced the stemness of cultured mouse corneal epithelial stem/progenitor cells (TKE2) in vitro, as shown by elevated clone formation ability and increased expression of stemness markers (especially p63 and SOX2). The contribution of ascorbic acid on the stemness enhancement was not dependent on the promotion of Akt phosphorylation, as concluded by using Akt inhibitor, nor was the stemness found to be dependent on the regulation of oxidative stress, as seen by the use of two other antioxidants (GMEE and NAC). However, ascorbic acid was found to promote extracellular matrix (ECM) production, and by using two collagen synthesis inhibitors (AzC and CIS), the increased expression of p63 and SOX2 by ascorbic acid was decreased by around 50%, showing that the increased stemness by ascorbic acid can be attributed to its regulation of ECM components. Moreover, the expression of p63 and SOX2 was elevated when TKE2 cells were cultured on collagen I coated plates, a situation that mimics the in vivo situation as collagen I is the main component in the corneal stroma. This study shows direct therapeutic benefits of ascorbic acid on corneal epithelial wound healing and provides new insights into the mechanisms involved. Stem Cells Translational Medicine 2017;6:1356-1365.
authors.affiliation: Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden.
authors.forename: Jialin
authors.initials: J
authors.lastname: Chen
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: Jie
authors.initials: J
authors.lastname: Lan
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: Dongle
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden.
authors.forename: Ludvig J
authors.initials: LJ
authors.lastname: Backman
authors.affiliation: Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
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.affiliation: Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden.|Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Danielson
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D003315:Cornea / Q000166:cytology*; D019573:Epithelium, Corneal / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D001205:Ascorbic Acid
keywords: Colony formation; Microenvironment; Proliferation; Stem cell-microenvironment interactions; Stem/progenitor cell; Tissue regeneration