Shulman K, Rosen S, Tognazzi K, Manseau E J, Brown L F
Department of Pathology, Beth Israel Hospital, Boston, MA 02215, USA.
J Am Soc Nephrol. 1996 May;7(5):661-6. doi: 10.1681/ASN.V75661.
Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a potent enhancer of microvascular permeability and a selective endothelial cell growth factor. In normal human kidney, VPF/VEGF mRNA and protein are strongly expressed by visceral glomerular epithelial cells, and VPF/VEGF may be an important regulator of glomerular endothelial cell function. This study examined 47 renal biopsies from patients with a variety of glomerular diseases for expression of VPF/VEGF mRNA and protein by in situ hybridization and immunohisto-chemistry. In many glomerular diseases, VPF/VEGF-expressing cells were decreased in number or absent in areas of focal or global glomerular sclerosis. Decreased numbers of VPF/VEGF-expressing cells in glomeruli were also noted in amyloidosis, diabetes, crescentic glomerulonephritis, and diffuse endocapillary proliferative glomerulonephritis associated with systemic lupus erythematosus. Normally, release of VPF/ VEGF must be under strict control because it is some 50,000 times more potent than histamine as an inducer of microvascular permeability. Damage to visceral epithelial cells in a variety of glomerular diseases has the potential for releasing relatively large amounts of VPF/VEGF locally, leading to increased glomerular permeability. In addition, because VPF/ VEGF is also an endothelial growth factor, the loss of normal, controlled secretion of VPF/VEGF after damage to visceral epithelial cells could lead to important alterations in glomerular endothelial cell function.
血管通透性因子(VPF),也被称为血管内皮生长因子(VEGF),是微血管通透性的强效增强剂和一种选择性内皮细胞生长因子。在正常人类肾脏中,VPF/VEGF信使核糖核酸(mRNA)和蛋白质由肾小球脏层上皮细胞强烈表达,并且VPF/VEGF可能是肾小球内皮细胞功能的重要调节因子。本研究通过原位杂交和免疫组织化学检查了47例患有各种肾小球疾病患者的肾活检组织中VPF/VEGF mRNA和蛋白质的表达情况。在许多肾小球疾病中,表达VPF/VEGF的细胞数量减少或在局灶性或全球性肾小球硬化区域中缺失。在淀粉样变性、糖尿病、新月体性肾小球肾炎以及与系统性红斑狼疮相关的弥漫性毛细血管内增生性肾小球肾炎中,也注意到肾小球中表达VPF/VEGF的细胞数量减少。正常情况下,VPF/VEGF的释放必须受到严格控制,因为作为微血管通透性诱导剂,它比组胺的效力约强50000倍。在各种肾小球疾病中,脏层上皮细胞受损有可能在局部释放相对大量的VPF/VEGF,导致肾小球通透性增加。此外,由于VPF/VEGF也是一种内皮生长因子,脏层上皮细胞受损后VPF/VEGF正常的、受控制的分泌丧失可能导致肾小球内皮细胞功能发生重要改变。