Linkoping大學(xué)的研究人員目前正在推行一項計劃,，以有效地治療牛皮癬,。約300萬瑞士人正遭受疾病治療的困難,，這表現(xiàn)在皮膚上的鱗屑和經(jīng)常性發(fā)癢。原因在于當深層皮膚內(nèi)心血管形成時細胞分裂沒有克制,。
一個重要的組分是psoriasin蛋白（S100A7）,，它豐富地存在于牛皮癬影響的皮膚里，但在正常的皮膚里很少有,。這個蛋白還被認為與乳腺癌的形成有關(guān),。由Charlotta Enerback副教授領(lǐng)導(dǎo)的研究小組在一項研究中已經(jīng)闡明，在培養(yǎng)的皮膚細胞中,，psoriasin,、氧自由基和血管內(nèi)皮生長因子(VEGF)的相互作用導(dǎo)致顯著增加的細胞分裂和新生血管的生長（血管增生）。當我們阻斷psoriasis的形成時,，VEGF的表達也降低了,。研究結(jié)果發(fā)表于《乳腺癌研究和治療》（ Breast Cancer Research and Treatment）期刊上,，此研究為這種致殘疾病的有效治療開辟了新的可能性。
"我們想測試psoriasis作為治療靶標的能力,。通過抑制psoriasis,，我們相信我們能減少血管的形成從而降低疾病擴散的廣度和強度，"Charlotta Enerback說,。之前在小鼠中的研究顯示,，血管生成抑制劑不僅能減少新生血管的形成，還能減少炎癥和過度的細胞分裂,。試圖抑制生長因子的嘗試結(jié)果造成了很多不必要的副作用,，因為它在正常組織中也存在并有助于傷口的愈合。
"由于psoriasis只在患銀屑病的皮膚中表達,，我們期望psoriasis抑制劑能夠選擇性高效性的治療這種疾病,，并且副作用的風(fēng)險最小。"
目前,，使用姑息療法結(jié)合維生素D,、可的松，輕及低劑量的化療,。最近,，一些"生物的"基于抗體的藥物抵達市場，然而它們都非常昂貴且有副作用,。（生物谷bioon.com）
doi:10.1007/s10549-011-1920-5
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Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation.
Emman Shubbar, Jenny Vegfors, Maria Carlström, Stina Petersson, Charlotta Enerbäck.
Abstract： Psoriasin (S100A7), originally identified in psoriasis, is a calcium-binding protein belonging to the multigenic S100 family. In high-grade ductal carcinoma in situ, psoriasin was identified as one of the most abundant transcripts. We have previously shown that psoriasin was induced by reactive oxygen species (ROS). Moreover, the downregulation of psoriasin by short hairpin RNA (shRNA) led to the reduced expression of vascular endothelial growth factor (VEGF) and inhibited tumor growth in vivo. The aim of the present study was to investigate whether psoriasin could have direct effects on endothelial cells. In this study we demonstrated that psoriasin increased VEGF expression in mammary epithelial cells. The treatment of endothelial cells with recombinant psoriasin increased proliferation comparable to that of recombinant VEGF protein. No change in proliferation was seen when endothelial cells were infected with psoriasin-expressing adenoviruses, suggesting that the proliferative effect of psoriasin was mediated by a specific receptor. Treatment with sRAGE, targeting the receptor for advanced glycation end products (RAGE), thus inhibited endothelial cell proliferation and tube formation enhanced by recombinant psoriasin. We showed that VEGF expression was not induced by hydrogen peroxide, when psoriasin was silenced by shRNA, which led to the hypothesis that psoriasin induces ROS. Indeed, psoriasin was shown to induce ROS in both endothelial and epithelial cells. Moreover, sRAGE inhibited the psoriasin-dependent generation of ROS in endothelial cells. Finally, treatment with antioxidant Bcl-2 protein abolished the effect of psoriasin on endothelial cell proliferation. Our data suggest that psoriasin expression in mammary epithelial cells leads to increased endothelial cell proliferation in a paracrine manner through RAGE. Psoriasin may therefore play a role in breast cancer progression by promoting oxidative stress response and angiogenesis.
