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Co-regulation of Cxcl1 and Versican in inflammatory response in UVB induced reactive oxygen species in the skin.

ABSTRACT: Reactive oxygen species (ROS) induced by ultraviolet B (UVB) cause DNA damage such as 8-oxoguanine (8-oxoG) in mouse skin, with long-term exposure leading skin tumor development. We previously reported that Ogg1 knockout mice, with defective repair enzyme for 8-oxoG oxidatively damaged DNA, showed greater up-regulation of inflammatory response genes and Versican, which encodes a large extracellular matrix proteoglycan, than their wild-type counterparts. Here, we focused on inflammatory response genes associated with Versican up-regulation after UVB exposure, using Ogg1 knockout mouse embryonic fibroblasts (MEFs). Gene profiling among inflammatory response-associated genes in MEFs treated with UVB showed that Cxcl1, a CXC chemokine, was most significantly up-regulated in Ogg1(-/-) MEFs, concomitant with the up-regulation of Versican. We found that Versican targeted siRNA directly regulated Cxcl1, and vice versa, in which the system of up-regulation for these two key genes were controlled by PI3kinase-NFkB activation signaling rather than conventional UV-induced p38 mitogen-activated protein kinase. Furthermore, for the initial process of differentiating inflammatory response between Ogg1(-/-) and Ogg1(+/+), we found that down-regulation of p53 along with anti-apoptotic signal was a key event in Ogg1(-/-).The results of the present study suggest suppression of skin tumor development involving UVB/ROS-induced 8-oxoG formation by targeting genes and signaling pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE80362 | GEO | 2016/04/25

SECONDARY ACCESSION(S): PRJNA318743

REPOSITORIES: GEO

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