Jin D K, Fish A J, Wayner E A, Mauer M, Setty S, Tsilibary E, Kim Y
Department of Pediatrics, Samsung Medical Center, Seoul, Korea.
J Am Soc Nephrol. 1996 Dec;7(12):2636-45. doi: 10.1681/ASN.V7122636.
Integrins are cell-surface protein receptors that participate in cell adhesion to multiple extracellular matrix ligands, and consist of alpha and beta chain heterodimers. This study examined altered integrin distribution in diabetic nephropathy by investigating 12 human diabetic kidney biopsies, which were compared with normal human kidney. Diabetic nephropathy is characterized by mesangial expansion and progressive thickening of the glomerular basement membrane. Based on morphometric studies of mesangial expansion, diabetic nephropathy was determined to be moderate or severe. Three different patterns (P) of altered intensity of integrin staining were observed. In the mesangial integrin P, the intensity of integrin subunit staining of mesangial cells (alpha 1, alpha 2, alpha 3, beta 1, alpha V, alpha V beta 5) was increased in moderate diabetic nephropathy and further increased in severe diabetic nephropathy. In the epithelial integrin P, integrin subunits localized to epithelial cells (alpha V, beta 3, alpha V beta 3, alpha V beta 5) were increased to the same extent in moderate and severe diabetic nephropathy. In the endothelial integrin P, integrin subunits localized to endothelial cells (alpha 3, alpha 5, alpha 6, beta 1) were increased in moderate diabetic nephropathy but returned to normal kidney staining intensity in severe diabetic nephropathy. From these observations, it was concluded that there is significant alteration in the expression of integrin subunits in diabetic nephropathy that is related to the severity of diabetic mesangial expansion. Additionally, the spectrum of integrin subunit alteration appears to be unique to individual glomerular cell types. Given the role of integrins in cell-surface interactions with extracellular matrix components, abnormalities in the expression of these molecules may be important in the pathogenesis of diabetic nephropathy.
整合素是细胞表面蛋白受体，参与细胞与多种细胞外基质配体的黏附，由α链和β链异二聚体组成。本研究通过对12例人类糖尿病肾活检组织进行研究，检测糖尿病肾病中整合素分布的改变，并与正常人类肾脏进行比较。糖尿病肾病的特征是系膜扩张和肾小球基底膜逐渐增厚。基于系膜扩张的形态计量学研究，确定糖尿病肾病为中度或重度。观察到整合素染色强度改变的三种不同模式（P）。在系膜整合素P中，系膜细胞（α1、α2、α3、β1、αV、αVβ5）的整合素亚基染色强度在中度糖尿病肾病中增加，在重度糖尿病肾病中进一步增加。在上皮整合素P中，定位于上皮细胞的整合素亚基（αV、β3、αVβ3、αVβ5）在中度和重度糖尿病肾病中增加程度相同。在内皮整合素P中，定位于内皮细胞的整合素亚基（α3、α5、α6、β1）在中度糖尿病肾病中增加，但在重度糖尿病肾病中恢复到正常肾脏染色强度。从这些观察结果得出结论，糖尿病肾病中整合素亚基的表达存在显著改变，这与糖尿病系膜扩张的严重程度有关。此外，整合素亚基改变的谱似乎对于单个肾小球细胞类型是独特的。鉴于整合素在细胞表面与细胞外基质成分相互作用中的作用，这些分子表达的异常可能在糖尿病肾病的发病机制中起重要作用。
