Podocyte expression of nonmuscle myosin heavy chain-IIA decreases in idiopathic nephrotic syndrome, especially in focal segmental glomerulosclerosis.
Podocyte expression of nonmuscle myosin heavy chain-IIA decreases in idiopathic nephrotic syndrome, especially in focal segmental glomerulosclerosis.
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DOI：
10.1093/ndt/gft350
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发表时间：
2013-12
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通讯作者：
K. Miura;H. Kurihara;S. Horita;H. Chikamoto;M. Hattori;Y. Harita;Haruko Tsurumi;Yuko Kajiho;Y. Sawada;S. Sasaki;T. Igarashi;S. Kunishima;T. Sekine
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作者：
K. Miura;H. Kurihara;S. Horita;H. Chikamoto;M. Hattori;Y. Harita;Haruko Tsurumi;Yuko Kajiho;Y. Sawada;S. Sasaki;T. Igarashi;S. Kunishima;T. Sekine
背景先前的研究已经发现特发性局灶节段性肾小球硬化(FSGS)的发生与Myh9编码的非肌肉肌球蛋白重链IIA(NMMHC-IIA)之间存在显著的相关性。然而，这些研究主要集中在Myh9基因多态性与FSGS发生发展的关系上。NMMHC-IIA在人类肾小球疾病中的病理变化尚未见报道。在此，我们报道了NMMHC-IIA在足细胞中的精确定位以及NMMHC-IIA在大鼠和人类病理状态下的表达变化。方法采用免疫细胞化学方法(免疫荧光和免疫电子显微镜)对NMMHC-IIA进行精确定位。研究了氨基核苷(PAN)处理的大鼠肾小球中NMMHC-IIA的表达水平，以及NMMHC-IIA和其他足细胞相关蛋白在特发性FSGS和其他重型蛋白尿性肾小球疾病患者肾小球中的表达水平。结果NMMHC-IIA主要定位于足细胞的胞体和初级突起，这一定位有别于其他引起遗传性FSGS的足细胞相关分子。在PAN处理的大鼠肾脏中，足细胞中NMMHC-IIA的表达水平降低。免疫组织化学分析显示，NMMHC-IIA在特发性肾病综合征尤其是FSGS中的表达水平显著降低，而在其他表现为明显蛋白尿的慢性肾小球肾炎中表达水平无明显变化。NMMHC-IIA在肾小球的表达发生了变化，而neparin和synaptopodin的表达保持不变。结论NMMHC-IIA在特发性肾病综合征，尤其是FSGS中的特异性表达降低，提示NMMHC-IIA在FSGS的发生发展中具有重要作用。
BACKGROUND Previous studies have identified significant associations between the development of idiopathic focal segmental glomerulosclerosis (FSGS) and MYH9 encoding nonmuscle myosin heavy chain-IIA (NMMHC-IIA). However, these studies focused only on the linkage of MYH9 polymorphisms and development of FSGS. There have been no reports on pathological changes of NMMHC-IIA in human glomerular diseases. Here we report on the precise localization of NMMHC-IIA in podocytes and changes in NMMHC-IIA expression in pathological states in rats and humans. METHODS Immunocytochemical (immunofluorescence and immunoelectron microscopy) studies were performed to determine the precise localization of NMMHC-IIA. Expression levels of NMMHC-IIA were investigated in puromycin aminonucleoside (PAN)-treated rats; and expression levels of NMMHC-IIA and other podocyte-related proteins were investigated in glomeruli of patients with idiopathic FSGS and other heavy proteinuric glomerular diseases. RESULTS NMMHC-IIA was located primarily at the cell body and primary processes of podocytes; this localization is distinct from other podocyte-related molecules causing hereditary FSGS. In PAN-treated rat kidneys, expression levels of NMMHC-IIA in podocytes decreased. Immunohistochemical analysis revealed that expression levels of NMMHC-IIA markedly decreased in idiopathic nephrotic syndrome, especially FSGS, whereas it did not change in other chronic glomerulonephritis showing apparent proteinuria. Changes in NMMHC-IIA expression were observed in glomeruli where expression of nephrin and synaptopodin was maintained. CONCLUSIONS Considering previous genome-wide association studies and development of FSGS in patients with MYH9 mutations, the characteristic localization of NMMHC-IIA and the specific decrease in NMMHC-IIA expression in idiopathic nephrotic syndrome, especially FSGS, suggest the important role of NMMHC-IIA in the development of FSGS.