Redistribution of connexin43 expression in glomerular podocytes predicts poor renal prognosis in patients with type 2 diabetes and overt nephropathy.
Redistribution of connexin43 expression in glomerular podocytes predicts poor renal prognosis in patients with type 2 diabetes and overt nephropathy.
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DOI：
10.1093/ndt/gfl260
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发表时间：
2006-09
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通讯作者：
K. Sawai;M. Mukoyama;K. Mori;H. Yokoi;M. Koshikawa;T. Yoshioka;Ryuji Takeda;A. Sugawara;T. Kuwahara;M. Saleem;O. Ogawa;K. Nakao
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作者：
K. Sawai;M. Mukoyama;K. Mori;H. Yokoi;M. Koshikawa;T. Yoshioka;Ryuji Takeda;A. Sugawara;T. Kuwahara;M. Saleem;O. Ogawa;K. Nakao
背景足细胞损伤在糖尿病肾病进展中的意义尚不清楚。在这项研究中，我们研究了足细胞中间隙连接蛋白connexin43 （Cx43）表达的改变是否与显性糖尿病肾病的进展有关。方法：我们招募了29例伴有显性肾病的2型糖尿病患者进行肾活检。7例局部肿瘤患者的肾切除标本和5例诊断为轻微肾小球异常的患者的活检标本作为对照。免疫组织化学对石蜡包埋肾切片进行Cx43染色。结果：在对照组中，Cx43在足细胞中沿肾小球基底膜呈线性表达。相比之下，在糖尿病肾病中，足细胞中Cx43的均匀线性染色下调和丧失（Cx43异质性）。Cx43的强度与当前肾功能相关（R = 0.647, P < 0.005），而Cx43异质性的大小与未来肾功能下降的程度相关（R = -0.705, P < 0.001）。结论：足细胞中Cx43表达的改变与显性糖尿病肾病的进展密切相关。这些结果表明，足细胞中Cx43表达的变化代表了显性糖尿病肾病的一个进展阶段，这可能是预测未来肾功能下降的一种方便的方法。
BACKGROUND Significance of podocyte injury in the progression of diabetic nephropathy is not well-understood. In this study, we examined whether alteration of gap junction protein connexin43 (Cx43) expression in podocytes is associated with the progression of overt diabetic nephropathy. METHODS We recruited 29 type 2 diabetic patients with overt nephropathy who underwent renal biopsy. Nephrectomized kidney samples obtained from seven subjects with localized neoplasm and biopsy specimens from five patients diagnosed as minor glomerular abnormalities were used as controls. Cx43 staining on paraffin-embedded kidney sections were studied by immunohistochemistry. RESULTS In controls, Cx43 was expressed at podocytes in a linear pattern along the glomerular basement membrane. In contrast, downregulation and loss of uniformly linear staining of Cx43 (Cx43 heterogeneity) in podocytes were observed in diabetic nephropathy. Cx43 intensity correlated with current renal function (R = 0.647, P < 0.005), whereas the magnitude of Cx43 heterogeneity correlated well with the degree of future decline in renal function (R = -0.705, P < 0.001). CONCLUSIONS Alteration of Cx43 expression in podocytes was closely associated with the progression of overt diabetic nephropathy. These results indicate that change in Cx43 expression at podocytes represents a progressive stage in overt diabetic nephropathy and that it may be a convenient way to predict future decline in renal function.