Hafdi Z, Lesavre P, Nejjari M, Halbwachs-Mecarelli L, Droz D, Noël L H
INSERM U 507, Department of Nephrology, Necker Hospital, Paris, France.
Cell Adhes Commun. 2000;7(6):441-51. doi: 10.3109/15419060009040302.
The alphav integrins present on the membrane of numerous cells, mediate attachment to matrix proteins, cell proliferation, migration and survival. We studied the expression of alphav integrinis and CD47 (a beta3 chain integrin associated protein) in various forms of glomerulonephritis (GN) characterized by mesangial proliferation and/or increased mesangial matrix. In normal glomeruli, epithelial cells expressed alphavbeta3, alphavbeta5 and CD47; endothelial cells expressed alpha5beta1 and CD47; mesangial cells expressed alphavbeta5, CD47, and to a less extent alphavbeta3. In acute post infectious GN (APIGN), membrano-proliferative GN (MPGN) and diabetic nephropathy(DN), we observed that the beta3 chain, normally expressed by mesangial cells, was not detectable in the mesangium while its expression by epithelial cells was not modified. Parallel to the disappearance of alphavbeta3, the CD47 expression was decreased on the mesangial cells in MPGN, APIGN and DN. The expression of alphavbeta5 was clearly increased on podocytes and on proliferating mesangial cells in APIGN. By contrast, the mesangial expression of alphavbeta was normal or decreased in DN. The alpha5 chain of integrin, absent on normal mesangial cell, was expressed on proliferating mesangial cells in MPGN and APIGN. Thus, we observed modifications of alphavbeta3 and alphavbeta5 expression during human GN. The modulations of alphavbeta3 and alphavbeta5 expression differed according to the different glomerular cell types and were not parallel in glomerular cells: alphavbeta3 was decreased (and alphavbeta5 unchanged) on proliferating mesangial cells and alphavbeta5 was increased (and alphavbeta3 unchanged) in podocytes. This may reflect the existence of two distinct regulatory pathways.
众多细胞表面存在的αv整合素介导细胞与基质蛋白的附着、细胞增殖、迁移及存活。我们研究了αv整合素及CD47(一种与β3链整合素相关的蛋白)在以系膜增殖和/或系膜基质增加为特征的各种形式肾小球肾炎(GN)中的表达。在正常肾小球中,上皮细胞表达αvβ3、αvβ5和CD47;内皮细胞表达α5β1和CD47;系膜细胞表达αvβ5、CD47,且αvβ3表达较少。在急性感染后肾小球肾炎(APIGN)、膜增生性肾小球肾炎(MPGN)和糖尿病肾病(DN)中,我们观察到系膜细胞通常表达的β3链在系膜中无法检测到,而上皮细胞对其表达未发生改变。与αvβ3消失同时,MPGN、APIGN和DN中系膜细胞上的CD47表达降低。在APIGN中,足细胞和增殖的系膜细胞上αvβ5的表达明显增加。相比之下,DN中系膜αvβ的表达正常或降低。正常系膜细胞上不存在的整合素α5链在MPGN和APIGN增殖的系膜细胞上表达。因此,我们观察到人类GN过程中αvβ3和αvβ5表达的改变。αvβ3和αvβ5表达的调节因肾小球细胞类型不同而不同,在肾小球细胞中并非平行变化:增殖的系膜细胞上αvβ3降低(αvβ5不变),足细胞中αvβ5增加(αvβ3不变)。这可能反映了存在两种不同的调节途径。