Naito Shokichi, Pippin Jeffrey W, Shankland Stuart J
Division of Nephrology Department of Medicine, University of Washington School of Medicine, Box 356521, 1959 NE Pacific St,, Seattle, WA 98195-6521, USA.
BMC Nephrol. 2014 Nov 6;15:174. doi: 10.1186/1471-2369-15-174.
Studies have shown in several diseases initially affecting podocytes, that the neighboring glomerular parietal epithelial cells (PECs) are secondarily involved. The PEC response might be reparative under certain circumstances, yet injurious under others. The factors governing these are not well understood. We have shown that SM22α, an actin-binding protein considered a marker of smooth muscle differentiation, is upregulated in podocytes and PECs in several models of podocyte disease. However, the impact of SM22α levels on PECs is not known.
Experimental glomerular disease, characterized by primary podocyte injury, was induced in aged-matched SM22α+/+ and SM22α-/-mice by intraperitoneal injection of sheep anti-rabbit glomeruli antibody. Immunostaining methods were employed on days 7 and 14 of disease.
The number of PEC transition cells, defined as cells co-expressing a PEC protein (PAX2) and podocyte protein (Synaptopodin) was higher in diseased SM22α-/-mice compared with SM22α+/+mice. WT1 staining along Bowman's capsule is higher in diseased SM22α-/-mice. This was accompanied by increased PEC proliferation (measured by ki-67 staining), and an increase in immunostaining for the progenitor marker NCAM, in a subpopulation of PECs in diseased SM22α-/-mice. In addition, immunostaining for vimentin and alpha smooth muscle actin, markers of epithelial-to-mesenchymal transition (EMT), was lower in diseased SM22α-/-mice compared to diseased SM22α+/+mice.
SM22α levels may impact how PECs respond following a primary podocyte injury in experimental glomerular disease. Absent/lower levels favor an increase in PEC transition cells and PECs expressing a progenitor marker, and a lower EMT rate compared to SM22α+/+mice, where SM22 levels are markedly increased in PECs.
研究表明，在几种最初影响足细胞的疾病中，相邻的肾小球壁层上皮细胞（PEC）会继发受累。PEC反应在某些情况下可能具有修复作用，但在其他情况下则具有损伤作用。对此起作用的因素尚不清楚。我们已经表明，SM22α是一种肌动蛋白结合蛋白，被认为是平滑肌分化的标志物，在几种足细胞疾病模型的足细胞和PEC中表达上调。然而，SM22α水平对PEC的影响尚不清楚。
通过腹腔注射羊抗兔肾小球抗体，在年龄匹配的SM22α+/+和SM22α-/-小鼠中诱导以原发性足细胞损伤为特征的实验性肾小球疾病。在疾病的第7天和第14天采用免疫染色方法。
与SM22α+/+小鼠相比，患病的SM22α-/-小鼠中，共表达PEC蛋白（PAX2）和足细胞蛋白（突触素）的PEC过渡细胞数量更多。患病的SM22α-/-小鼠沿鲍曼囊的WT1染色更高。这伴随着PEC增殖增加（通过ki-67染色测量），以及患病的SM22α-/-小鼠中一部分PEC中祖细胞标志物NCAM的免疫染色增加。此外，与患病的SM22α+/+小鼠相比，患病的SM22α-/-小鼠中波形蛋白和α平滑肌肌动蛋白（上皮-间质转化（EMT）的标志物）的免疫染色更低。
在实验性肾小球疾病中，SM22α水平可能会影响原发性足细胞损伤后PEC的反应。与SM22α+/+小鼠相比，SM22α缺失/水平较低有利于PEC过渡细胞和表达祖细胞标志物的PEC增加，且EMT率较低，在SM22α+/+小鼠中，PEC中的SM22水平显著增加。
