title: Ribonuclease 5 facilitates corneal endothelial wound healing via activation of PI3-kinase/Akt pathway.
abstract: To maintain corneal transparency, corneal endothelial cells (CECs) exert a pump function against aqueous inflow. However, human CECs are arrested in the G1-phase and non-proliferative in vivo. Thus, treatment of corneal endothelial decompensation is limited to corneal transplantation, and grafts are vulnerable to immune rejection. Here, we show that ribonuclease (RNase) 5 is more highly expressed in normal human CECs compared to decompensated tissues. Furthermore, RNase 5 up-regulated survival of CECs and accelerated corneal endothelial wound healing in an in vitro wound of human CECs and an in vivo cryo-damaged rabbit model. RNase 5 treatment rapidly induced accumulation of cytoplasmic RNase 5 into the nucleus, and activated PI3-kinase/Akt pathway in human CECs. Moreover, inhibition of nuclear translocation of RNase 5 using neomycin reversed RNase 5-induced Akt activation. As a potential strategy for proliferation enhancement, RNase 5 increased the population of 5-bromo-2'-deoxyuridine (BrdU)-incorporated proliferating CECs with concomitant PI3-kinase/Akt activation, especially in CECs deprived of contact-inhibition. Specifically, RNase 5 suppressed p27 and up-regulated cyclin D1, D3, and E by activating PI3-kinase/Akt in CECs to initiate cell cycle progression. Together, our data indicate that RNase 5 facilitates corneal endothelial wound healing, and identify RNase 5 as a novel target for therapeutic exploitation.
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Korea.|Graduate School of Chung-Ang University, College of Medicine, Seoul, Korea.
authors.forename: Kyoung Woo
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Korea.
authors.forename: Jae Chan
authors.initials: JC
authors.lastname: Kim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D004722:Endoribonucleases / Q000378:metabolism*; D004728:Endothelium, Corneal / Q000473:pathology*; D004789:Enzyme Activation; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011817:Rabbits; D014945:Wound Healing
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D004722:Endoribonucleases; C025115:ribonuclease V