Floege J, Hudkins K L, Davis C L, Schwartz S M, Alpers C E
Division of Nephrology, Medizinische Hochschule, Hannover, Germany.
J Am Soc Nephrol. 1998 Feb;9(2):211-23. doi: 10.1681/ASN.V92211.
Platelet-derived growth factor (PDGF) plays an important role in renal disease. We have recently demonstrated that in healthy mature human kidney, PDGF alpha-receptor expression is largely restricted to interstitial cells. The study presented here assesses the expression of PDGF alpha-receptor in 18 mature adult kidneys with arteriosclerosis from individuals with no clinically evident history of renal disease other than localized neoplasia, in 13 kidneys with irreversible transplant rejection, and in a series of renal transplant biopsies composed of examples of both severe and absent rejection, by in situ hybridization and immunocytochemistry. Strong focal or diffuse expression of PDGF alpha-receptor mRNA and protein was noted in some intimal cells of intrarenal arterial vessels exhibiting signs of arteriosclerosis and/or vascular rejection. By double immunostaining, it could be shown that these cells were neither endothelial cells nor infiltrating leukocytes. The cells were most often identified as smooth muscle by colabeling for the smooth muscle cell-specific protein SM22alpha and less commonly for alpha-smooth muscle actin. There was also a population of PDGF alpha-receptor-expressing cells that failed to colabel with any of these markers, and hence remain of uncertain histogenesis. These intimal cells were generally negative for several other markers of differentiated smooth muscle cells, i.e., calponin and desmin. Near these PDGF alpha-receptor-positive intimal cells, expression of PDGF A-chain, an alpha-receptor ligand, was demonstrated in endothelial, intimal, and/or medial cells. Prominent PDGF alpha-receptor mRNA and protein expression also was noted in areas of interstitial fibrosis and in some glomeruli, in particular those with segmental glomerulosclerosis or fibrotic crescents. Double immunolabeling for PDGF alpha-receptor and alpha-smooth muscle actin confirmed that most of these latter PDGF alpha-receptor-positive cells were interstitial myofibroblasts or mesangial cells, or both. In summary, these data demonstrate widespread expression of PDGF alpha-receptor in renal cell types involved in fibrotic and sclerosing processes. The data also show that PDGF alpha-receptor expression identifies a unique population of phenotypically altered vascular smooth muscle cells, which appear to be involved in the vascular response to injury.
血小板衍生生长因子（PDGF）在肾脏疾病中起重要作用。我们最近证明，在健康成熟的人肾脏中，PDGFα受体的表达主要局限于间质细胞。本文介绍的研究通过原位杂交和免疫细胞化学方法，评估了18例无除局限性肿瘤外临床明显肾脏疾病病史的成年动脉硬化患者的成熟肾脏、13例不可逆移植排斥反应患者的肾脏以及一系列包括严重排斥和无排斥反应实例的肾移植活检组织中PDGFα受体的表达情况。在表现出动脉硬化和/或血管排斥迹象的肾内动脉血管的一些内膜细胞中，观察到PDGFα受体mRNA和蛋白的强烈局灶性或弥漫性表达。通过双重免疫染色可以表明，这些细胞既不是内皮细胞也不是浸润性白细胞。通过对平滑肌细胞特异性蛋白SM22α进行共标记，这些细胞最常被鉴定为平滑肌细胞，较少被鉴定为α平滑肌肌动蛋白。也有一群表达PDGFα受体的细胞未能与这些标志物中的任何一种进行共标记，因此其组织发生仍不确定。这些内膜细胞通常对几种其他分化平滑肌细胞标志物呈阴性，即钙调蛋白和平滑肌肌动蛋白。在这些PDGFα受体阳性内膜细胞附近，在内皮细胞、内膜细胞和/或中膜细胞中证实了PDGF A链（一种α受体配体）的表达。在间质纤维化区域和一些肾小球中，特别是那些有节段性肾小球硬化或纤维化新月体的肾小球中，也观察到显著的PDGFα受体mRNA和蛋白表达。对PDGFα受体和α平滑肌肌动蛋白进行双重免疫标记证实，这些后一种PDGFα受体阳性细胞大多数是间质肌成纤维细胞或系膜细胞，或两者皆有。总之，这些数据证明了PDGFα受体在参与纤维化和硬化过程的肾细胞类型中广泛表达。数据还表明，PDGFα受体表达可识别一群表型改变的血管平滑肌细胞，这些细胞似乎参与了血管对损伤的反应。
