| First Author | Chen L | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 3 | Pages | e0151869 |
| PubMed ID | 26987064 | Mgi Jnum | J:249075 |
| Mgi Id | MGI:6093217 | Doi | 10.1371/journal.pone.0151869 |
| Citation | Chen L, et al. (2016) Corneal Wound Healing Requires IKB kinase beta Signaling in Keratocytes. PLoS One 11(3):e0151869 |
| abstractText | IkB kinase beta (IKKbeta) 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 IKKbeta in the cornea using Ikkbeta(DeltaCS) mice in which the Ikkbeta gene was specifically deleted in the corneal stromal keratocytes. The Ikkbeta(DeltaCS) corneas had normal morphology, transparency and thickness; however, they did not heal well from mild alkali burn injury. In contrast to the Ikkbeta(F/F) corneas that restored transparency in 2 weeks after injury, over 50% of the Ikkbeta(DeltaCS) 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 alpha smooth muscle actin (alpha-SMA) expression, higher levels of senescence beta-Gal activity and scar tissue formation at the late stage of wound healing. In addition, the Ikkbeta(DeltaCS) 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 IKKbeta in keratocytes is required to repress oxidative stress and attenuate fibrogenesis and senescence in corneal wound healing. |
