Expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in chronic glomerulonephritis, especially IgA glomerulonephritis

肾小球系膜细胞的增殖常见于肾小球肾炎如伊加肾小球肾炎。最近的报告表明，脑/胚胎型肌球蛋白亚型（MIIB 2）参与细胞增殖。我们已经研究了MIIB 2的表达在肾活检样品中的患者与各种肾脏疾病和肾组织中的大鼠模型的系膜增生性肾小球肾炎诱导抗Thy 1.1抗体。使用抗脑型肌球蛋白重链特异性单克隆抗体（HBM 1）的活检样本的免疫组织化学分析表明，92%的伊加肾小球肾炎患者的样本中含有大量的系膜细胞与抗体反应。来自其他类型的增生性肾小球疾病患者的大多数样品也含有HBM 1反应性系膜细胞，而来自非增生性肾小球疾病患者的样品均不含有显著的HBM 1反应性系膜细胞群体。注射抗Thy 1.1的大鼠在注射抗体后第5天开始在系膜细胞中表达增加水平的脑/胚胎型肌球蛋白重链同种型（MIIB 2），并持续表达同种型直至第10天。另一方面，系膜细胞中增殖细胞不明抗原的表达在注射抗Thy 1.1抗体后3天被诱导，并且在第4天达到最大。注射抗Thy 1.1抗体后约5天，诱导I型胶原（肾小球的主要细胞外基质组分）的表达。这些结果表明，系膜细胞的MIIB 2亚型的表达在增殖性肾小球肾炎中加速，并表明肌球蛋白亚型参与肾小球组织的表型转化，而不是细胞增殖。

Proliferation of mesangial cells is frequently found in glomerulonephritis such as IgA glomerulonephritis. Recent reports suggest that a brain/embryo-type myosin isoform (MIIB2) is involved in cell proliferation. We have studied the expression of MIIB2 in renal biopsy samples from patients with various renal diseases and in the renal tissues from the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Immunohistochemical analysis of the biopsy samples using an anti-brain-type myosin heavy chain-specific monoclonal antibody (HBM1) indicated that 92% of the samples from patients with IgA glomerulonephritis contained a significant population of mesangial cells that reacted with the antibody. Most of sample from patients with other types of proliferative glomerular diseases also contained HBM1-reactive mesangial cells, while none of the samples from patients with non-proliferative glomerular diseases contained a significant population of HBM1-reactive mesangial cells. The anti-Thy 1.1-injected rats began to express an increased level of a brain/embryo-type myosin heavy chain isoform (MIIB2) in the mesangial cells at 5 days after injection of the antibody and continued to express the isoform up to the 10th day. On the other hand, the expression of the proliferating cell unclear antigen in the mesangial cells was induced at 3 days after injection of anti-Thy 1.1 antibody and was maximal at the 4th day. The expression of type I collagen, a major extracellular matrix component of the glomeruli, was induced about 5 days after injection of the anti-Thy 1.1 antibody. These results indicate that the expression of the MIIB2 isoform by mesangial cells is accelerated in proliferative glomerulonephritis and suggest that the myosin isoform is involved in the phenotypic transformations of the glomerular tissues rather than in the cell proliferation.