title: Corneal Wound Healing Requires IKB kinase β Signaling in Keratocytes.
abstract: IkB kinase β (IKKβ) is a key signaling kinase for inflammatory responses, but it also plays diverse cell type-specific roles that are not yet fully understood. Here we investigated the role of IKKβ in the cornea using Ikkβ(ΔCS) mice in which the Ikkβ gene was specifically deleted in the corneal stromal keratocytes. The Ikkβ(ΔCS) corneas had normal morphology, transparency and thickness; however, they did not heal well from mild alkali burn injury. In contrast to the Ikkβ(F/F) corneas that restored transparency in 2 weeks after injury, over 50% of the Ikkβ(ΔCS) corneas failed to fully recover. They instead developed recurrent haze with increased stromal thickness, severe inflammation and apoptosis. This pathogenesis correlated with sustained myofibroblast transformation with increased α smooth muscle actin (α-SMA) expression, higher levels of senescence β-Gal activity and scar tissue formation at the late stage of wound healing. In addition, the Ikkβ(ΔCS) corneas displayed elevated expression of hemo-oxygenase-1 (HO-1), a marker of oxidative stress, and activation of stress signaling pathways with increased JNK, c-Jun and SMAD2/3 phosphorylation. These data suggest that IKKβ in keratocytes is required to repress oxidative stress and attenuate fibrogenesis and senescence in corneal wound healing.
authors.affiliation: Department of Environmental Health and Center of Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267-0056, United States of America.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Environmental Health and Center of Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267-0056, United States of America.
authors.forename: Maureen
authors.initials: M
authors.lastname: Mongan
authors.affiliation: Department of Environmental Health and Center of Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267-0056, United States of America.
authors.forename: Qinghang
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Environmental Health and Center of Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267-0056, United States of America.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267-0056, United States of America.
authors.forename: Winston
authors.initials: W
authors.lastname: Kao
authors.affiliation: Department of Environmental Health and Center of Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267-0056, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003315:Cornea / Q000378:metabolism / Q000503:physiopathology; D065306:Corneal Injuries / Q000150:complications / Q000503:physiopathology*; D060527:Corneal Keratocytes / Q000378:metabolism / Q000502:physiology*; D003318:Corneal Opacity / Q000209:etiology / Q000503:physiopathology; D051550:I-kappa B Kinase / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D058628:Myofibroblasts / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D051550:I-kappa B Kinase