TY  - THES
A1  - Kahlina, Kornelija
T1  - P68 RNA helicase : a novel mediator of nitric oxide and mitogen functions in keratinocytes
N2  - Nitric oxide (NO) represents a short-lived mediator that pivotally drives keratinocyte movements during cutaneous wound healing. In this study, we have identified p68 DEAD box RNA helicase (p68) from a NO-induced differential keratinocyte cDNA library. Subsequently, we have analyzed regulation of p68 by wound-associated mediators in the human keratinocyte cell line HaCaT. NO, serum, growth factors and pro-inflammatory cytokines were potent inducers of p68 expression in the cells. p68 was constitutively expressed in murine skin, but rapidly down-regulated upon injury. The down-regulation appeared to be transient, as p68 protein expression increased again after the inflammatory phase of repair. However, p68 protein expression did not completely disappear during wound inflammation, as immunohistochemistry and cell fractiona tion analysis revealed a restricted localization of p68 in keratinocyte nuclei of the developing epithelium. In line, cultured human (HaCaT) and murine (PAM 212) keratinocyte cell lines showed a nuclear localization of the helicase. Moreover, confocal microscopy revealed a strong localization of p68 protein within the nucleoli of the keratinocytes. Functional analyses demonstrated that p68 strongly participates in keratinocyte proliferation and gene expression. Keratinocytes that constitutively overexpressed p68 protein were characterized by a marked increase in serum-induced proliferation and vascular endothelial growth factor (VEGF) expression, whereas down-regulation of endogenous p68 using small interfering RNA (siRNA) markedly attenuated serum-induced proliferation and VEGF expression. Altogether, our results suggest a tightly controlled expression and nucleolar localization of p68 in keratinocytes in vitro and during skin repair in vivo that functionally contributes to keratinocyte proliferation and gene expression.
Y1  - 2004
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/5015
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-0000004809
N1  - The work outlined in this thesis is based on experimental studies published in the following article: Kahlina K, Goren I, Pfeilschifter J, Frank S:  p68 DEAD box RNA helicase expression in keratinocytes: regulation, nuclear localization, and functional connection to proliferation and VEGF gene expression. J Biol Chem 279: 44872-44882, 2004
CY  - Frankfurt am Main
ER  -