Simonetti O, Lucarini G, Goteri G, Zizzi A, Biagini G, Lo Muzio L, Offidani A
Clinica Dermatologica, Università Politecnica delle Marche, Ancona, Italy.
Int J Immunopathol Pharmacol. 2006 Oct-Dec;19(4):751-60. doi: 10.1177/039463200601900405.
Psoriasis is a chronic skin disease, characterized by epidermal hyperplasia, inflammation, angiogenesis and vascular remodelling. An immunohistochemical study on fifteen cryosections of psoriatic skin was performed using antibodies against VEGF, HIF1-alpha, CD34, Factor VIII, MMP-2, MMP-9, TIMP-1 and TIMP-2. Psoriatic skin showed a diffuse VEGF positive staining (13.15+/-6.6), while no expression was observed in normal epidermis. No or faint HIF-1alpha immunostaining was detected in healthy skin, while in psoriatic skin HIF-1alpha was diffusely expressed. A positive correlation between HIF-1alpha and VEGF was reported in psoriatic skin (r= 0.644; p=0.010). In psoriatic sections CD34 expression was significantly higher in respect to control skin (19.15+/-12.61 vs 3.0+/-0.23; p= 0.04), factor VIII immunostaining also demonstrated a significant increased development of the microvasculature in comparison with healthy skin (18.39+/-8.16 vs 7.4+/-0.20; p= 0.033). Total MMP-2 expression of healthy skin (30+/-2.26) was significantly lower in respect to the MMP-2 psoriatic skin (71.5+/-4.13; p= 0.0001) and a positive correlation was observed between VEGF and MMP-2 in psoriatic patients (r= 0.688; p= 0.046). In psoriatic skin MMP-9 expression was significantly increased in comparison to control skin (31+/-3.3 vs 8+/-6.1; p=0.007). All cases of psoriatic skin tissue showed that TIMP-2 and TIMP-1 expression statistically decreased in psoriatic skin (respectively 11+/-1.2 and 12+/-1.5) in comparison with healthy skin (respectively 15+/-3.2 and 53+/-3.8; p=0.0001). In conclusion, we observed that VEGF overexpression correlated with HIF-1alpha and MMP-2 expression, underlining the role of VEGF in psoriasis as a key factor in the link between inflammation and angiogenesis.
银屑病是一种慢性皮肤病,其特征为表皮增生、炎症、血管生成和血管重塑。使用抗VEGF、HIF1-α、CD34、因子VIII、MMP-2、MMP-9、TIMP-1和TIMP-2的抗体,对15个银屑病皮肤冰冻切片进行了免疫组织化学研究。银屑病皮肤呈现弥漫性VEGF阳性染色(13.15±6.6),而在正常表皮中未观察到表达。在健康皮肤中未检测到或仅检测到微弱的HIF-1α免疫染色,而在银屑病皮肤中HIF-1α呈弥漫性表达。据报道,银屑病皮肤中HIF-1α与VEGF之间存在正相关(r = 0.644;p = 0.010)。在银屑病切片中,CD34表达相对于对照皮肤显著升高(19.15±12.61对3.0±0.23;p = 0.04),因子VIII免疫染色也显示与健康皮肤相比,微血管的发育显著增加(18.39±8.16对7.4±0.20;p = 0.033)。健康皮肤的总MMP-2表达(30±2.26)相对于银屑病皮肤的MMP-2显著降低(71.5±4.13;p = 0.0001),并且在银屑病患者中观察到VEGF与MMP-2之间存在正相关(r = 0.688;p = 0.046)。与对照皮肤相比,银屑病皮肤中MMP-9表达显著增加(31±3.3对8±6.1;p = 0.007)。所有银屑病皮肤组织病例均显示,与健康皮肤相比,银屑病皮肤中TIMP-2和TIMP-1表达在统计学上降低(分别为11±1.2和12±1.5)(分别为15±3.2和53±3.8;p = 0.0001)。总之,我们观察到VEGF过表达与HIF-1α和MMP-2表达相关,强调了VEGF在银屑病中作为炎症与血管生成之间联系的关键因素的作用。