School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Histopathology. 2011 Sep;59(3):397-406. doi: 10.1111/j.1365-2559.2011.03970.x.
To investigate the expression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors and decoy receptors, including osteoprotegerin (OPG) in infantile haemangioma (IH).
Immunostaining, Western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used on IH biopsies and haemangioma explant-derived cells (HaemEDCs). TRAIL and its receptors and decoy receptors, including OPG, are expressed in proliferating IH tissues and in HaemEDCs. Cells forming the endothelium of immature capillaries of proliferating IHs express abundant OPG and show punctate von Willebrand Factor (vWF) staining. As the cells mature and assume the characteristic of endothelial cells they increase expression of vWF, but lose expression of OPG. The endothelium of IH shows minimal expression of receptor activator for nuclear factor кB ligand (RANKL) compared with a small population of RANKL-positive cells located within the interstitium between microvessels. Proliferating HaemEDCs express significantly higher levels of OPG and decoy receptor 2 than the matched tissue samples. Increased OPG expression is detected in the extracellular matrix and in the conditioned medium of HaemEDCs.
Our data suggest that OPG through the TRAIL pathway, but not the RANKL pathway, plays a role in regulating anti-apoptosis during the development of IH.
研究肿瘤坏死因子相关凋亡诱导配体(TRAIL)及其受体和诱饵受体,包括骨保护素(OPG)在婴儿血管瘤(IH)中的表达。
采用免疫组化、Western blot 和定量逆转录聚合酶链反应(qRT-PCR)检测 IH 活检组织和血管瘤衍生细胞(HaemEDCs)中 TRAIL 及其受体和诱饵受体,包括 OPG 的表达。TRAIL 及其受体和诱饵受体,包括 OPG,在增殖性 IH 组织和 HaemEDCs 中表达。形成增殖性 IH 不成熟毛细血管内皮的细胞表达丰富的 OPG,并显示点状 von Willebrand 因子(vWF)染色。随着细胞成熟并表现出内皮细胞的特征,它们增加 vWF 的表达,但失去 OPG 的表达。与位于微血管之间间质内的一小部分 RANKL 阳性细胞相比,IH 的内皮细胞表达的核因子кB 配体受体激活剂(RANKL)很少。增殖的 HaemEDCs 表达的 OPG 和诱饵受体 2 明显高于匹配的组织样本。在 HaemEDCs 的细胞外基质和条件培养基中检测到 OPG 表达增加。
我们的数据表明,OPG 通过 TRAIL 途径,而不是 RANKL 途径,在 IH 发育过程中调节抗凋亡作用。