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β1和β3整合素在快速进展性肾小球肾炎中的上调

Beta 1 and beta 3 integrin upregulation in rapidly progressive glomerulonephritis.

作者信息

Baraldi A, Zambruno G, Furci L, Ballestri M, Tombesi A, Ottani D, Lucchi L, Lusvarghi E

机构信息

Department of Nephrology, University of Modena, Italy.

出版信息

Nephrol Dial Transplant. 1995;10(7):1155-61.

PMID:7478117
Abstract

The expression and distribution pattern of beta 1 (alpha 1-alpha 6) and alpha v beta 3 integrins and ICAM-1 and VCAM-1 counter receptors were evaluated by an immunohistochemical technique on eight renal samples from patients affected by rapidly progressive glomerulonephritis (RPGN) of different aetiologies. In all cases integrins and counterreceptors displayed similar patterns. On tubular cells of renal cortex, a marked upregulation of alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 3 integrins and VCAM-1 was observed with as many as 60-90% of tubular cross-sections labelled, while a strong ICAM-1 reactivity was limited to the luminal surface. The same adhesion molecules were also uniformly expressed on crescentic cells. In glomeruli, integrin upregulation occurred only on apparently preserved capillary tufts, i.e. in an early stage of lesion, while collapsed and sclerotic tufts showed a reduced integrin expression. In addition a morphometric study of extracellular matrix (EM) proteins cellular fibronectin and tenascin showed a 9.56 +/- 1.9-fold and 3.35 +/- 0.6-fold increase respectively in these proteins, as compared to normal kidney (P < 0.001). The upregulation of alpha v beta 3 on podocytes might play a role in the adhesion of crescentic cells. An increased production of cytokines, in particular transforming growth factor-beta, might induce augmented deposition of EM proteins and upregulation of beta 1 and beta 3 integrins in RPGN.

摘要

采用免疫组织化学技术,对8例不同病因的快速进行性肾小球肾炎(RPGN)患者的肾组织样本进行检测,评估β1(α1-α6)和αvβ3整合素以及细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)等配体的表达及分布模式。在所有病例中,整合素及其配体均呈现相似的模式。在肾皮质的肾小管细胞上,观察到α2β1、α3β1、α5β1、αvβ3整合素和VCAM-1显著上调,多达60%-90%的肾小管横断面有标记,而ICAM-1的强反应仅限于管腔表面。同样的黏附分子在新月体细胞上也呈均匀表达。在肾小球中,整合素上调仅出现在明显保留的毛细血管袢上,即病变早期,而塌陷和硬化的袢则显示整合素表达降低。此外,对细胞外基质(EM)蛋白、细胞纤连蛋白和腱生蛋白的形态计量学研究显示,与正常肾脏相比,这些蛋白分别增加了9.56±1.9倍和3.35±0.6倍(P<0.001)。足细胞上αvβ3的上调可能在新月体细胞的黏附中起作用。细胞因子尤其是转化生长因子-β的产生增加,可能诱导RPGN中EM蛋白沉积增加以及β1和β3整合素上调。

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