C10orf99 contributes to the development of psoriasis by promoting the proliferation of keratinocytes.
C10orf99 contributes to the development of psoriasis by promoting the proliferation of keratinocytes.
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C10orf99 通过促进角质形成细胞增殖促进牛皮癣的发展
DOI：
10.1038/s41598-018-26996-z
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发表时间：
2018-06-05
影响因子：
4.6
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Chen C;Wu N;Duan Q;Yang H;Wang X;Yang P;Zhang M;Liu J;Liu Z;Shao Y;Zheng Y
牛皮癣是一种慢性、复发性炎症性皮肤病。银屑病的发病机制复杂，目前尚不完全清楚。C10orf99是新近发现的一种人类抗菌肽，其在银屑病患者皮肤样本中表达上调。在这项研究中，我们研究了C10orf99在炎症条件下表皮增殖中的功能作用。我们发现C10orf99蛋白在银屑病患者的皮肤样本中显著上调，并且在咪喹莫特(Imiquimod，ImQ)诱导的小鼠银屑病样皮肤皮损中，正相关基因的表达水平上调。利用M5刺激的HaCaT细胞炎症模型和C10orf99基因敲除和过表达相结合的方法，我们证明C10orf99可以促进角质形成细胞的增殖，促进角质形成细胞的G1/S转变，C10orf99的促增殖作用与ERK1/2和NF-κB的激活有关，而与AKT通路无关。表达C10orf99 shRNA的慢病毒载体局部耗尽C10orf99可有效改善ImQ诱导的皮炎。综上所述，这些结果表明C10orf99在银屑病的发病机制中起着重要作用，可能成为银屑病治疗的新靶点。
Psoriasis is a chronic, relapsing inflammatory skin disease. The pathogenesis of psoriasis is complex and has not been fully understood. C10orf99 was a recently identified human antimicrobial peptide whose mRNA expression is elevated in psoriatic human skin samples. In this study, we investigated the functional roles of C10orf99 in epidermal proliferation under inflammatory condition. We showed that C10orf99 protein was significantly up-regulated in psoriatic skin samples from patients and the ortholog gene expression levels were up-regulated in imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. Using M5-stimulated HaCaT cell line model of inflammation and a combinational approach of knockdown and overexpression of C10orf99, we demonstrated that C10orf99 could promote keratinocyte proliferation by facilitating the G1/S transition, and the pro-proliferation effect of C10orf99 was associated with the activation of the ERK1/2 and NF-κB but not the AKT pathways. Local depletion of C10orf99 by lentiviral vectors expressing C10orf99 shRNA effectively ameliorated IMQ-induced dermatitis. Taken together, these results indicate that C10orf99 plays a contributive role in psoriasis pathogenesis and may serve as a new target for psoriasis treatment.
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影响因子：
30.8
作者：
Nair RP;Duffin KC;Helms C;Ding J;Stuart PE;Goldgar D;Gudjonsson JE;Li Y;Tejasvi T;Feng BJ;Ruether A;Schreiber S;Weichenthal M;Gladman D;Rahman P;Schrodi SJ;Prahalad S;Guthery SL;Fischer J;Liao W;Kwok PY;Menter A;Lathrop GM;Wise CA;Begovich AB;Voorhees JJ;Elder JT;Krueger GG;Bowcock AM;Abecasis GR;Collaborative Association Study of Psoriasis
通讯作者：
Collaborative Association Study of Psoriasis
影响因子：
24.1
作者：
通讯作者：
--
影响因子：
3.5
作者：
Hirsch, Tobias;Spielmann, Malte;Eriksson, Elof
通讯作者：
Eriksson, Elof
影响因子：
5.8
作者：
Li, Xiaoling;Fan, Rangrang;Guo, Gang
通讯作者：
Guo, Gang
影响因子：
78.5
作者：
Bresnick, Anne R.;Weber, David J.;Zimmer, Danna B.
通讯作者：
Zimmer, Danna B.