银屑病患者骨髓CD34+细胞Notch受体及其靶基因表达的研究

中华皮肤科杂志 ›› 2011, Vol. 44 ›› Issue (3): 168-170.

银屑病患者骨髓CD34+细胞Notch受体及其靶基因表达的研究

侯瑞霞¹,李俊琴¹,刘瑞风¹,李新华¹,张静²,尹国华¹,张开明¹

1. 太原市中心医院皮肤科
2. 太原市中心医院内科

收稿日期:2010-06-21 修回日期:2010-07-26 出版日期:2011-03-15 发布日期:2011-03-10
通讯作者: 张开明 E-mail:zhangkaiming@sina.com
基金资助:
国家自然基金

Expressions of Notch receptors and target genes in bone marrow CD34+ cells from patients with psoriasis

Received:2010-06-21 Revised:2010-07-26 Online:2011-03-15 Published:2011-03-10

摘要/Abstract

摘要：

目的探讨银屑病患者骨髓CD34+细胞表面两种Notch受体的表达及其下游靶基因Hes-1的表达。方法分离12例银屑病患者及10例正常对照骨髓CD34+细胞，以β-肌动蛋白为内参照，采用Western印迹法半定量检测Notch受体1、2及其下游靶基因Hes-1的蛋白表达水平。结果银屑病患者CD34+造血细胞Notch1表达水平（0.9488 ± 0.3221）明显高于正常人对照（0.6693 ± 0.1465）；Hes-1蛋白在银屑病患者表达（0.8579 ± 0.3729）亦高于正常人对照（0.5728 ± 0.1787），两者差异均有统计学意义（P < 0.05），而Notch2蛋白的表达在患者组（0.7568 ± 0.3461）和正常人对照组（0.8312 ± 0.2887）之间差异无统计学意义（P > 0.05）。结论 Notch1受体及其下游基因Hes-1的高表达可能参与银屑病患者骨髓造血细胞低增殖活性的发生。

关键词: Hes-1

Abstract:

Objective To study the expressions of Notch receptors （Notch1 and 2） and target gene Hes-1 in bone marrow CD34+ cells from patients with psoriasis. Methods CD34+ cells were isolated from the bone marrow of 12 patients with psoriasis and 19 normal human controls. Western blot was conducted to detect the expressions of Notch1, Notch2 and Hes-1 proteins in CD34+ cells, with the house-keeping gene β-actin as an internal reference. Results In contrast with normal controls, a significant increment was observed in the expressions of Notch1 and Hes-1 proteins in psoriatic patients （0.9488 ± 0.3221 vs. 0.6693 ± 0.1465, 0.8579 ± 0.3729 vs. 0.5728 ± 0.1787, both P < 0.05）. No significant difference was observed in the expression of Notch2 between psoriatic patients and normal controls （0.7568 ± 0.3461 vs. 0.8312 ± 0.2887, P > 0.05）. Conclusion The over expression of Notch1 and Hes-1 may be associated with the low proliferation activity of psoriatic hematopoietic cells.

Key words: Hes-1

侯瑞霞李俊琴刘瑞风李新华张静尹国华张开明. 银屑病患者骨髓CD34+细胞Notch受体及其靶基因表达的研究[J]. 中华皮肤科杂志, 2011, 44(3): 168-170.

参考文献

1. 牛旭平，李新华，张开明等. 银屑病患者骨髓造血细胞体外增殖活性研究. 中国皮肤病性病杂志，2007,21（04）：196-198. 2. Zhang Kaiming, Li Xinhua, Yin Guohua, et al. Functional characterization of CD4+CD25+ regulatory T cells differentiated in vitro from bone marrow-derived haematopoietic cells of psoriasis patients with a family history of the disorder. British Journal of Dermatology, 2008, 158:298–305. 3. 牛旭平，徐海涛，尹国华等.银屑病患者单一核细胞培养上清对骨髓造血干细胞和祖细胞集落形成的影响.中华皮肤科杂志,2006,39:143-145. 4. 尹国华，李新华，张开明等. 银屑病患者骨髓CD34+细胞体外定向分化T细胞的研究. 中华皮肤科杂志，2006，39：124-127. 5. Zhang K, Zhang R, Li X, et al. The mRNA expression and promoter methylation status of the p16 gene in colony-forming cells with high proliferative potential in patients with psoriasis. Clinical and Experimental dermatology, 2007, 32(2): 702-708. 6. K. Zhang, R. Hou, X. Niu, et al.Decreased colony formation of high proliferative potential colony-forming cells and granulocyte-macrophage colony-forming units and increased Hes-1 expression in bone marrow mononuclear cells from patients with psoriasis. British Journal of Dermatology, 已定稿（BJD9790）. 7. Artavanis-Tsakonas S, Matsuno K, Fortini ME: Notch signaling. Science. 1995, 68:225. 8. Egan SE, St Pierre B, Leow CC: Notch receptors, partners and regulators: From conserved domains to powerful functions. Curr Top Microbiol Immunol.1998, 228: 273. 9. Milner LA and Bigas A. Notch as a Mediator of Cell Fate Determination in Hematopoiesis: Evidence and Speculation. Blood, 1999, 93(8): 2431-2448. 10. Castella P, Sawai S, Nakao K, et al. HES-1 Repression of Differentiation and Proliferation in PC12 Cells: Role for the Helix 3-Helix 4 Domain in Transcription Repression. Molecular and Cellular Biology, 2000, 20(16): 6170-6183. 11. 侯瑞霞，尹国华，李新华等．银屑病患者骨髓CD34+细胞Notch受体的表达．中华微生物学和免疫学杂志，2009，29：212． 12. 侯瑞霞，尹国华，李俊琴等．银屑病患者骨髓CD34+细胞Hes-1基因的表达研究．临床皮肤科杂志，2009，38，619-621． 13. 李新华; 张开明; 尹国华等. 银屑病患者骨髓CD34+细胞定向分化的T细胞对角质形成细胞增殖的影响. 临床皮肤科杂志,2008,37(6):348-350. 14. Li Xinhua, Fan Xing, Zhang Kaiming, et al. In?uence of psoriatic peripheral blood CD4+ T and CD8+ T lymphocytes on C-myc, Bcl-xL and Ki67 gene expression in keratinocytes. Eur J Dermatol 2007; 17 (5): 1-5. 15. 张开明,李新华. 骨髓,银屑病的发病“中枢”? 中国皮肤性病学杂志, 2004,18：501-503. 16. Milner LA, Kopan R, Martin DI, et al. A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors. Blood 83:2057, 1994 17. Lam LT, Ronchini C, Norton J, et al. Suppression of Erythroid but Not Megakaryocytic Differentiation of Human K562 Erythroleukemic Cells by Notch-1. J. Biol. Chem., 2000, 275, (26): 19676-19684. 18. Neves H, Weerkamp F, Gomes AC. et al. Effects of Delta1 and Jagged1 on Early Human Hematopoiesis: Correlation with Expression of Notch Signaling-Related Genes in CD34+ Cells. Stem Cells, 2006, 24 (5): 1328-1337. 19. Bigas A, Martin DIK, Milner LA: Notch1 and Notch2 inhibit myeloid differentiation in response to different cytokines. Mol Cell Biol 1998，18:2324. 20. Atsushi K, Shigeru C, Etsuko NY, et al. HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo. Blood, 2003, 101(5): 1777-1783.