Defect of IL17 Signaling, but Not Centrinone, Inhibits the Development of Psoriasis and Skin Papilloma in Mouse Models.
Defect of IL17 Signaling, but Not Centrinone, Inhibits the Development of Psoriasis and Skin Papilloma in Mouse Models.
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DOI：
10.3390/biomedicines10081976
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发表时间：
2022-08-15
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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银屑病患者容易发展为皮肤癌，表皮增生是银屑病和皮肤鳞状细胞癌（SCC）的组织病理学标志，表明它们可能具有共同的致病机制。白细胞介素-17 （IL17）刺激表皮增生，导致牛皮癣。控制中心粒复制的polo样激酶4 （PLK4）在SCC中被发现过表达，这也显示了角化细胞的过度增殖。为了研究il - 17信号通路与中心粒复制在表皮增生中的协同作用，我们建立了野生型（WT）、il - 17受体A （T779A）敲除蛋白（Il17ra(T779A)-KI）和il - 17受体C敲除蛋白（Il17rc-KO）小鼠银屑病和皮肤乳头瘤模型。采用生物信息学、Western blot、免疫组化染色、集落形成、real-time PCR等方法检测il - 17信号通路和centrinone对上皮细胞增殖的影响。在银屑病模型中，与WT和Il17ra(T779A)-KI相比，Il17rc-KO显著抑制表皮增厚。从WT到Il17ra(T779A)-KI和Il17rc-KO小鼠，角质形成细胞的增殖明显降低。在皮肤乳头瘤模型中，与WT相比，Il17ra(T779A)-KI显著降低了肿瘤负荷，而Il17ra - ko则消除了乳头瘤的发展。然而，PLK4的选择性抑制剂centrinone在两种模型中都没有影响皮肤病变的形成。我们的数据表明，Il17ra(T779A)-KI和Il17rc-KO可以预防皮肤银屑病的发展和肿瘤的发生，而局部给药则没有任何效果。
Patients with psoriasis tend to develop skin cancer, and the hyperproliferation of the epidermis is a histopathological hallmark of both psoriasis and cutaneous squamous cell carcinoma (SCC), indicating that they may share pathogenic mechanisms. Interleukin-17 (IL17) stimulates the proliferation of the epidermis, leading to psoriasis. Overexpression of Polo-like kinase 4 (PLK4), which controls centriole duplication, has been identified in SCC, which also shows the hyperproliferation of keratinocytes. To investigate the cooperation between IL17 signaling and centriole duplication in epidermal proliferation, we established psoriasis and skin papilloma models in wild type (WT), IL17 receptor A (T779A) knockin (Il17ra(T779A)-KI), and IL17 receptor C knockout (Il17rc-KO) mouse strains. Bioinformatics, Western blot, immunohistochemical staining, colony formation, and real-time PCR were used to determine the effect of IL17 signaling and centrinone on epithelial proliferation. In the psoriasis model, compared to WT and Il17ra(T779A)-KI, Il17rc-KO dramatically suppressed epidermal thickening. The proliferation of keratinocytes significantly decreased in this order from WT to Il17ra(T779A)-KI and Il17rc-KO mice. In the skin papilloma model, Il17ra(T779A)-KI significantly decreased tumor burden compared to the WT, while Il17rc-KO abolished papilloma development. However, centrinone, a selective inhibitor of PLK4, did not affect skin lesion formation in either model. Our data demonstrated that Il17ra(T779A)-KI and Il17rc-KO prevent the development of psoriasis and tumorigenesis in the skin, while the topical administration of centrinone does not have any effect.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
DOI：
10.1038/jid.2009.65
发表时间：
2009-09
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
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影响因子：
5.7
作者：
Coates, Anthony R. M.;Hu, Yanmin;Yeh, Pamela
通讯作者：
Yeh, Pamela
影响因子：
--
作者：
Liu S;Zhang Q;Chen C;Ge D;Qu Y;Chen R;Fan YM;Li N;Tang WW;Zhang W;Zhang K;Wang AR;Rowan BG;Hill SM;Sartor O;Abdel-Mageed AB;Myers L;Lin Q;You Z
通讯作者：
You Z
影响因子：
4.4
作者：
Cheuk, Stanley;Wiken, Maria;Eidsmo, Liv
通讯作者：
Eidsmo, Liv