Linkoping大学的研究人员目前正在推行一项计划，以有效地治疗牛皮癣。约300万瑞士人正遭受疾病治疗的困难，这表现在皮肤上的鳞屑和经常性发痒。原因在于当深层皮肤内心血管形成时细胞分裂没有克制。
一个重要的组分是psoriasin蛋白（S100A7），它丰富地存在于牛皮癣影响的皮肤里，但在正常的皮肤里很少有。这个蛋白还被认为与乳腺癌的形成有关。由Charlotta Enerback副教授领导的研究小组在一项研究中已经阐明，在培养的皮肤细胞中，psoriasin、氧自由基和血管内皮生长因子(VEGF)的相互作用导致显著增加的细胞分裂和新生血管的生长（血管增生）。当我们阻断psoriasis的形成时，VEGF的表达也降低了。研究结果发表于《乳腺癌研究和治疗》（ Breast Cancer Research and Treatment）期刊上，此研究为这种致残疾病的有效治疗开辟了新的可能性。
"我们想测试psoriasis作为治疗靶标的能力。通过抑制psoriasis，我们相信我们能减少血管的形成从而降低疾病扩散的广度和强度，"Charlotta Enerback说。之前在小鼠中的研究显示，血管生成抑制剂不仅能减少新生血管的形成，还能减少炎症和过度的细胞分裂。试图抑制生长因子的尝试结果造成了很多不必要的副作用，因为它在正常组织中也存在并有助于伤口的愈合。
"由于psoriasis只在患银屑病的皮肤中表达，我们期望psoriasis抑制剂能够选择性高效性的治疗这种疾病，并且副作用的风险最小。"
目前，使用姑息疗法结合维生素D、可的松，轻及低剂量的化疗。最近，一些"生物的"基于抗体的药物抵达市场，然而它们都非常昂贵且有副作用。（生物谷bioon.com）
doi:10.1007/s10549-011-1920-5
PMC:
PMID:
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.
