| First Author | Chen L | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 1 | Pages | e16132 |
| PubMed ID | 21264230 | Mgi Jnum | J:180829 |
| Mgi Id | MGI:5307954 | Doi | 10.1371/journal.pone.0016132 |
| Citation | Chen L, et al. (2011) IkappaB kinase beta regulates epithelium migration during corneal wound healing. PLoS One 6(1):e16132 |
| abstractText | The IKKbeta is known to regulate transcription factor NF-kappaB activation leading to inflammatory responses. Recent gene knockout studies have shown that IKKbeta can orchestrate local inflammatory responses and regulate homeostasis of epithelial tissues. To investigate whether IKKbeta has an intrinsic role in epithelial cells, we established an in vivo system in the immune privileged corneal epithelium. We generated triple transgenic Krt12(rtTA/rtTAt)/tet-O-Cre/Ikkbeta(F/F) (Ikkbeta(DeltaCE/DeltaCE)) mice by crossing the Krt12-rtTA knock-in mice, which express the reverse tetracycline transcription activator in corneal epithelial cells, with the tet-O-Cre and Ikkbeta(F/F) mice. Doxycycline-induced IKKbeta ablation occurred in corneal epithelial cells of triple transgenic Ikkbeta(DeltaCE/DeltaCE) mice, but loss of IKKbeta did not cause ocular abnormalities in fetal development and postnatal maintenance. Instead, loss of IKKbeta significantly delayed healing of corneal epithelial debridement without affecting cell proliferation, apoptosis or macrophage infiltration. In vitro studies with human corneal epithelial cells (HCEpi) also showed that IKKbeta was required for cytokine-induced cell migration and wound closure but was dispensable for cell proliferation. In both in vivo and in vitro settings, IKKbeta was required for optimal activation of NF-kappaB and p38 signaling in corneal epithelial cells, and p38 activation is likely mediated through formation of an IKKbeta-p38 protein complex. Thus, our studies in corneal epithelium reveal a previously un-recognized role for IKKbeta in the control of epithelial cell motility and wound healing. |
