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未受累皮肤、急性针尖状皮损和已建立的银屑病斑块中的血管生成和淋巴管生成的组织学和转录组学研究:银屑病中血管发育时间进程的研究方法。

Histological and transcriptional study of angiogenesis and lymphangiogenesis in uninvolved skin, acute pinpoint lesions and established psoriasis plaques: an approach of vascular development chronology in psoriasis.

机构信息

Department of Dermatology, University Hospital of Liège, Belgium.

出版信息

J Dermatol Sci. 2010 Mar;57(3):162-9. doi: 10.1016/j.jdermsci.2009.12.006. Epub 2010 Jan 7.

DOI:10.1016/j.jdermsci.2009.12.006
PMID:20071151
Abstract

BACKGROUND

Dysregulation of angiogenesis and lymphangiogenesis could participate in psoriasis pathogenesis. Analysis of nascent psoriasis lesions should help at identifying early vascular anomalies.

OBJECTIVE

To analyse vascular development, angiogenesis and lymphangiogenesis markers expression in uninvolved skin in psoriatic patients (N), early psoriasis lesions or pinpoints (PP) and psoriasis plaques (PSO).

METHODS

Skin biopsies were taken in 17 patients in N and in PSO and/or PP. The mRNA steady-state level of angiogenesis and lymphangiogenesis markers was measured by RT-PCR. Immunohistochemistry was performed for von Willebrand factor, podoplanin, Ki-67 and VEGFR3. Blood (BV) and lymphatic (LV) vessels expansion was measured by computer-assisted morphometry.

RESULTS

Clinical and epidermal aspects indicated that PP are intermediate between N and PSO. While total BV area was already increased in PP similarly to PSO as compared to N, LV area in PP was intermediate between N and PSO. Mean LV size was identical in N and PP and increased in PSO, mean BV size in PP being intermediate between N and PSO. VEGF-A 189 variant was increased in PP as compared to N and PSO. As compared to N, angiogenesis markers (VEGF-A isoforms, PlGF, VEGFR2, NRP-1), VEGF-C and NRP-2 were similarly increased in PP and PSO. Keratin 16 and the lymphangiogenesis markers (VEGFR3, prox-1) were intermediate in PP.

CONCLUSION

These data suggest that the expansion of lymphatic vessels occurs after blood vascular development in psoriasis. Expansion of BV in PP could be followed by vessel enlargement during progression to PSO, in parallel with a decreased VEGF-A 189/VEGF-A 121 balance in plaques.

摘要

背景

血管生成和淋巴管生成的失调可能参与了银屑病的发病机制。分析初发银屑病皮损有助于发现早期血管异常。

目的

分析未受累皮肤、早期银屑病皮损或皮损点(PP)和银屑病斑块(PSO)中血管生成和淋巴管生成标志物的表达。

方法

在 17 例 N 期和 PSO 及/或 PP 患者中进行皮肤活检。采用 RT-PCR 法检测血管生成和淋巴管生成标志物的 mRNA 稳态水平。采用免疫组织化学法检测血管性血友病因子(von Willebrand factor,vWF)、足突蛋白(podoplanin)、Ki-67 和 VEGFR3。采用计算机辅助形态计量学检测血管(BV)和淋巴管(LV)扩张。

结果

临床和表皮表现表明,PP 介于 N 和 PSO 之间。与 N 相比,PP 中的总 BV 面积与 PSO 相似增加,而 PP 中的 LV 面积介于 N 和 PSO 之间。N 和 PP 中的 LV 大小相同,PSO 中增加,PP 中的 BV 大小介于 N 和 PSO 之间。与 N 相比,PP 中 VEGF-A189 变体增加,与 N 相比,PP 和 PSO 中血管生成标志物(VEGF-A 异构体、PlGF、VEGFR2、NRP-1)、VEGF-C 和 NRP-2 增加。在 PP 中,角蛋白 16 和淋巴管生成标志物(VEGFR3、prox-1)处于中间水平。

结论

这些数据表明,在银屑病中,淋巴管的扩张发生在血管生成之后。PP 中 BV 的扩张可能在进展为 PSO 时伴随着血管增大,而斑块中 VEGF-A189/VEGF-A121 平衡降低。

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