Chen H C, Chen C A, Guh J Y, Chang J M, Shin S J, Lai Y H
Department of Internal Medicine, Kaohsiung Medical University, Taiwan, ROC.
Life Sci. 2000 Sep 29;67(19):2345-53. doi: 10.1016/s0024-3205(00)00815-8.
The adhesion molecule integrin alpha3beta1 is the major receptor of podocyte to the glomerular capillary basement membrane (GBM). Since progressive alteration of the glomerular extracellular matrix (ECM) compartment leading to GBM thickening is common in diabetic nephropathy, we investigated the cellular distribution of alpha3beta1 integrin in podocytes of patients with diabetic nephropathy and streptozotocin-induced diabetic rats, and we evaluated the effects of high glucose on the cultured rat podocytes. Both human and rat kidneys were stained using the immunoelectron microscopy and immunoperoxidase technique with mouse monoclonal antibodies to human integrin alpha3 subunit. The results showed that both the number of immunogold particles and the staining of integrin alpha3 subunit on podocytes were weaker in patients with diabetic nephropathy than those of control kidneys. The staining of alpha3 on podocytes in the poorly-controlled diabetic rats was also weaker after one and three months of hyperglycemia. However, the staining was identical to controls in rats with only one week of hyperglycemia. High glucose (25 mM) but not streptozotocin in vitro suppressed the alpha3 expression of cultured rat podocytes. Our results demonstrated that the expression of integrin alpha3beta1 on podocytes was suppressed in both human and rats with diabetes, possibly due to the effects of hyperglycemia, and the suppression became more severe with the duration of diabetes.
黏附分子整合素α3β1是足细胞与肾小球毛细血管基底膜（GBM）的主要受体。由于在糖尿病肾病中，导致GBM增厚的肾小球细胞外基质（ECM）成分的进行性改变很常见，我们研究了糖尿病肾病患者和链脲佐菌素诱导的糖尿病大鼠足细胞中α3β1整合素的细胞分布，并评估了高糖对培养的大鼠足细胞的影响。使用针对人整合素α3亚基的小鼠单克隆抗体，通过免疫电子显微镜和免疫过氧化物酶技术对人和大鼠肾脏进行染色。结果显示，糖尿病肾病患者足细胞上的免疫金颗粒数量和整合素α3亚基的染色均比对照肾脏弱。在高血糖1个月和3个月后，血糖控制不佳的糖尿病大鼠足细胞上的α3染色也较弱。然而，仅高血糖1周的大鼠的染色与对照相同。体外高糖（25 mM）而非链脲佐菌素可抑制培养的大鼠足细胞的α3表达。我们的结果表明，糖尿病患者的人和大鼠足细胞上整合素α3β1的表达均受到抑制，这可能是高血糖的影响，并且随着糖尿病病程的延长，这种抑制变得更加严重。
