Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes
Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes
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DOI：
10.2337/diabetes.45.4.488
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发表时间：
1996-04-01
期刊：
影响因子：
7.7
通讯作者：
Nagai, R
中科院分区：
文献类型：
--
作者：
Makino, H;Kashihara, N;Nagai, R
肾小球系膜细胞表型的改变被认为在糖尿病肾病细胞外基质积聚中起关键作用。本研究旨在评估链脲佐菌素（STZ）诱导的糖尿病大鼠肾脏和糖尿病肾病患者肾活检标本中收缩蛋白的各种亚型的表达。使用肌球蛋白重链同种型（SM 1、SM 2、SMemb）、钙调蛋白和α-平滑肌肌动蛋白的特异性抗体以及SMemb的cDNA。在STZ给药后1周，SMemb在mRNA和蛋白水平的表达增加。这两个水平在4周时都有所增加。在4周时观察到钙调蛋白的系膜染色，在24周时观察到α-平滑肌肌动蛋白的系膜染色。糖尿病肾病患者肾小球系膜收缩蛋白的免疫组化染色明显，而正常对照组仅为微量系膜染色。这些结果表明，系膜细胞的表型变化发生在糖尿病的早期阶段，表型变化可能存在几个阶段。收缩蛋白亚型的表达，特别是SMemb，应该作为一个新的标志物，为随后的肾小球肥大和硬化。
The phenotypic change of the mesangial cell is considered to play a pivotal role in the accumulation of extracellular matrix in diabetic nephropathy. This investigation was undertaken to evaluate the expression of the various isoforms of contractile proteins in the streptozocin (STZ)-induced diabetic rat kidney and in renal biopsy specimens from patients with diabetic nephropathy. Specific antibodies to myosin heavy chain isoforms (SM1, SM2, SMemb), caldesmon, and alpha-smooth muscle actin and cDNAs for SMemb were used. Increased expression of SMemb at the mRNA and protein levels was demonstrated at 1 week after STZ administration in the rat. Both levels were increased at 4 weeks. Mesangial staining of caldesmon was observed at 4 weeks and that of alpha-smooth muscle actin at 24 weeks. Immunohistochemical mesangial staining of the contractile proteins was pronounced in patients with diabetic nephropathy in contrast to the trace mesangial staining in normal control subjects. These results indicate that the phenotypic change in mesangial cells occurs in the early stages of diabetes and that several stages in phenotypic changes may exist. Expression of the contractile protein isoforms, especially SMemb, should serve as a new marker for the subsequent glomerular hypertrophy and sclerosis.