Inhibition of CtBP-Regulated Proinflammatory Gene Transcription Attenuates Psoriatic Skin Inflammation.
Inhibition of CtBP-Regulated Proinflammatory Gene Transcription Attenuates Psoriatic Skin Inflammation.
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DOI：
10.1016/j.jid.2021.06.029
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Huang M
中科院分区：
文献类型：
--
作者：
Li H;Zhang C;Bian L;Deng H;Blevins M;Han G;Fan B;Yang C;Zhao R;High W;Norris D;Fujita M;Wang XJ;Huang M
Psoriasis is a chronic immune-mediated disease characterized by excessive proliferation of epidermal keratinocytes and increased immune cell infiltration to the skin. Although it is well known that psoriasis pathogenesis is driven by aberrant production of proinflammatory cytokines, the mechanisms underlying the imbalance between proinflammatory and anti-inflammatory cytokine expression are incompletely understood. Here we report that the transcriptional coregulators C-terminal-binding protein (CtBP) 1 and 2 can transactivate a common set of proinflammatory genes both in the skin of imiquimod-induced mouse psoriasis model and in human keratinocytes and macrophages stimulated by imiquimod. We find that mice overexpressing CtBP1 in epidermal keratinocytes display severe skin inflammation phenotypes with increased expression of Th1 and Th17 cytokines. We also find that the expression of CtBPs and CtBP target genes is elevated both in human psoriatic lesions and in the mouse imiquimod psoriasis model. Moreover, we were able to demonstrate that topical treatment with a peptidic inhibitor of CtBP effectively suppresses the CtBP-regulated proinflammatory gene expression and thus attenuates psoriatic inflammation in the imiquimod mouse model. Together, our findings suggest new strategies for therapeutic modulation of the immune response in inflammatory skin diseases.
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DOI：
10.1038/jid.2013.504
发表时间：
2014-05
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Deng H;Li F;Li H;Deng Y;Liu J;Wang D;Han G;Wang XJ;Zhang Q
通讯作者：
Zhang Q
影响因子：
9.8
作者：
Jordan, Catherine T.;Cao, Li;Bowcock, Anne M.
通讯作者：
Bowcock, Anne M.
影响因子：
4.8
作者：
Bellesis, Andrew G.;Jecrois, Anne M.;Royer, William E., Jr.
通讯作者：
Royer, William E., Jr.
ZnF750与KLF4和RCOR1，KDM1A和CTBP1/2染色质调节剂相互作用，以抑制表皮祖细胞基因并诱导分化基因。
影响因子：
10.5
作者：
Boxer LD;Barajas B;Tao S;Zhang J;Khavari PA
通讯作者：
Khavari PA
影响因子：
3.6
作者：
Dcona MM;Morris BL;Ellis KC;Grossman SR
通讯作者：
Grossman SR