Under-expression of VHL and over-expression of HDAC-1, HIF-1α, LL-37, and IAP-2 in affected skin biopsies of patients with psoriasis
Under-expression of VHL and over-expression of HDAC-1, HIF-1α, LL-37, and IAP-2 in affected skin biopsies of patients with psoriasis
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DOI：
10.1111/j.1365-4632.2006.02962.x
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发表时间：
2007-03-01
影响因子：
3.6
通讯作者：
Cancino-Diaz, Mario E.
中科院分区：
文献类型：
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作者：
Tovar-Castillo, Laura E.;Cancino-Diaz, Juan C.;Cancino-Diaz, Mario E.
背景银屑病的一个特征是角质形成细胞的快速增殖，在此期间细胞凋亡被阻断，血管生成开始。已知肿瘤缺氧细胞产生组蛋白脱乙酰酶-1（HDAC-1），其通过上调血管内皮生长因子（VEGF）表达来上调缺氧诱导因子-1 α（HIF-1 α）并下调von Hippel-Lindau（VHL）蛋白。最近有报道猪肽PR 39（与人LL-37同源）具有血管生成和抗凋亡活性。因此，胰岛素样生长因子-1（IGF-1）诱导的LL-37可能有助于VEGF的产生。PR 39还诱导细胞凋亡抑制蛋白-2（IAP-2）的表达，其阻断细胞凋亡。方法采用半定量逆转录聚合酶链反应（RT-PCR）和免疫组化方法，对银屑病患者和健康人皮肤活检组织中VHL、IAP-2及相关基因的表达进行研究。结果HDAC-1、HIF-1 α、IAP-2、VHL、IAP-2及相关基因在银屑病皮损组织中均呈高表达。结果显示，与健康人皮肤相比，银屑病患者皮肤中VHL、LL-37、IGF-1的表达明显降低，抗血管生成的VHL mRNA和蛋白在银屑病患者皮肤中低表达，而在健康人皮肤中高表达。抗凋亡IAP-2在银屑病皮肤真皮内皮细胞中过表达。促凋亡Bax，Fas和FasL的mRNAs的expressed.Conclusions这些研究结果表明，可能有一个协会HDAC-1，HIF-1 α，LL-37，VHL，IAP-2与银屑病血管生成和凋亡机制。
Background A feature of psoriasis is the rapid proliferation of keratinocytes, during which apoptosis is blocked and angiogenesis starts. It is known that tumor hypoxic cells produce histone deacetylase-1 (HDAC-1), which up-regulates hypoxia-inducible factor-1 alpha (HIF-1 alpha) and down-regulates von Hippel-Lindau (VHL) protein by up-regulating vascular endothelial growth factor (VEGF) expression. It has been reported recently that the porcine peptide PR39 (homologous to human LL-37) has angiogenic and antiapoptotic activity. Thus, LL-37, induced by insulin-like growth factor-1 (IGF-1), could help in the production of VEGF. PR39 also induces the expression of inhibitor of apoptosis protein-2 (IAP-2), which blocks apoptosis. The purpose of this work was to analyze whether these genes and their proteins are expressed in psoriatic biopsies.Methods Using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) messenger RNA (mRNA) expression and immunohistochemical staining, we studied VHL, IAP-2, and related genes in skin biopsies from psoriatic patients and healthy subjects.Results An over-expression of the mRNA for HDAC-1, HIF-1 alpha, LL-37, and IGF-1 in psoriatic skin, in comparison with skin from healthy subjects, was found. The antiangiogenic VHL mRNA and protein were under-expressed in psoriatic skin and highly expressed in healthy skin. The antiapoptotic IAP-2 was over-expressed in dermal endothelial cells from psoriatic skin. The pro-apoptotic Bax, Fas, and FasL mRNAs were expressed.Conclusions These findings suggest that there could be an association of HDAC-1, HIF-1 alpha, LL-37, VHL, and IAP-2 with angiogenic and apoptotic mechanisms in psoriasis.