Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis.
Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis.
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DOI：
10.1038/srep34690
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发表时间：
2016-10-04
影响因子：
4.6
通讯作者：
Oike Y
中科院分区：
文献类型：
--
作者：
Tanigawa H;Miyata K;Tian Z;Aoi J;Kadomatsu T;Fukushima S;Ogata A;Takeda N;Zhao J;Zhu S;Terada K;Endo M;Morinaga J;Sugizaki T;Sato M;Morioka MS;Manabe I;Mashimo Y;Hata A;Taketomi Y;Yamamoto K;Murakami M;Araki K;Jinnin M;Ihn H;Oike Y
牛皮癣是一种慢性炎症性皮肤病，其特征是异常的组织修复。突变小鼠银屑病皮肤特征的建模提供了有用的信息，相关的分子机制，并可用于评估治疗策略。在这里，我们发现表皮ANGPTL 6表达在小鼠组织修复过程中被显著诱导。对角质形成细胞中过表达ANGPTL 6的小鼠（K14-Angptl 6 Tg小鼠）的分析显示，由于过早分化的角质形成细胞的过度增殖，表皮ANGPTL 6活性促进异常的表皮屏障功能。此外，K14-Angptl 6 Tg小鼠的皮肤组织显示在银肩病中观察到的异常活化的皮肤组织炎症。最近提出作为银肩病治疗靶标的蛋白S100 A9的水平在K14-Angptl 6 Tg小鼠的皮肤组织中也增加，但这些小鼠中的银肩病样炎性表型不能通过S100 A9缺失来挽救。这一发现表明，降低S100 A9水平可能不会改善所有银屑病病例，并且该疾病的机制不同。最后，我们在一些银屑病患者的组织标本中观察到表皮ANGPTL 6水平的增强。我们得出结论，K14-Angptl 6 Tg小鼠可用于研究银屑病发病机制和用于新疗法的临床前测试。我们的研究还表明，角质形成细胞中的ANGPTL 6活化增强了银屑病易感性。
Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue repair. Mutant mice modeling psoriasis skin characteristics have provided useful information relevant to molecular mechanisms and could serve to evaluate therapeutic strategies. Here, we found that epidermal ANGPTL6 expression was markedly induced during tissue repair in mice. Analysis of mice overexpressing ANGPTL6 in keratinocytes (K14-Angptl6 Tg mice) revealed that epidermal ANGPTL6 activity promotes aberrant epidermal barrier function due to hyperproliferation of prematurely differentiated keratinocytes. Moreover, skin tissues of K14-Angptl6 Tg mice showed aberrantly activated skin tissue inflammation seen in psoriasis. Levels of the proteins S100A9, recently proposed as therapeutic targets for psoriasis, also increased in skin tissue of K14-Angptl6 Tg mice, but psoriasis-like inflammatory phenotypes in those mice were not rescued by S100A9 deletion. This finding suggests that decreasing S100A9 levels may not ameliorate all cases of psoriasis and that diverse mechanisms underlie the condition. Finally, we observed enhanced levels of epidermal ANGPTL6 in tissue specimens from some psoriasis patients. We conclude that the K14-Angptl6 Tg mouse is useful to investigate psoriasis pathogenesis and for preclinical testing of new therapeutics. Our study also suggests that ANGPTL6 activation in keratinocytes enhances psoriasis susceptibility.
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DOI：
10.1073/pnas.1531901100
发表时间：
2003-08-05
影响因子：
11.1
作者：
Oike, Y;Yasunaga, K;Suda, T
通讯作者：
Suda, T
DOI：
10.1038/jidsymp.2011.5
发表时间：
2011-12
影响因子：
--
作者：
Huggenberger, Reto;Detmar, Michael
通讯作者：
Detmar, Michael
影响因子：
7.2
作者：
Legry, V.;Goumidi, L.;Meirhaeghe, A.
通讯作者：
Meirhaeghe, A.
影响因子：
10.3
作者：
Gisondi, P.;Tessari, G.;Girolomoni, G.
通讯作者：
Girolomoni, G.
影响因子：
1.1
作者：
KARINIEMI, AL;VIRTANEN, I
通讯作者：
VIRTANEN, I