title: Ciliary Neurotrophic Factor Promotes the Migration of Corneal Epithelial Stem/progenitor Cells by Up-regulation of MMPs through the Phosphorylation of Akt.
abstract: The migration of limbal epithelial stem cells is important for the homeostasis and regeneration of corneal epithelium. Ciliary neurotrophic factor (CNTF) has been found to promote corneal epithelial wound healing by activating corneal epithelial stem/progenitor cells. However, the possible effect of CNTF on the migration of corneal epithelial stem/progenitor cells is not clear. This study found the expression of CNTF in mouse corneal epithelial stem/progenitor cells (TKE2) to be up-regulated after injury, on both gene and protein level. CNTF promoted migration of TKE2 in a dose-dependent manner and the peak was seen at 10 ng/ml. The phosphorylation level of Akt (p-Akt), and the expression of MMP3 and MMP14, were up-regulated after CNTF treatment both in vitro and in vivo. Akt and MMP3 inhibitor treatment delayed the migration effect by CNTF. Finally, a decreased expression of MMP3 and MMP14 was observed when Akt inhibitor was applied both in vitro and in vivo. This study provides new insights into the role of CNTF on the migration of corneal epithelial stem/progenitor cells and its inherent mechanism of Up-regulation of matrix metalloproteinases through the Akt signalling pathway.
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, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden.
authors.forename: Ludvig J
authors.initials: LJ
authors.lastname: Backman
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, 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; D002465:Cell Movement; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019573:Epithelium, Corneal / Q000166:cytology* / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020934:Ciliary Neurotrophic Factor; D051057:Proto-Oncogene Proteins c-akt; D020782:Matrix Metalloproteinases