Supplementary Material for: Glomerular Transcriptome Changes Associated with Lipopolysaccharide-Induced Proteinuria

<i>Background:</i> Global gene expression patterns have recently been characterized in normal glomeruli, but gene expression changes that accompany glomerular disease remain poorly characterized. <i>Method:</i> Here, we mapped global glomerular gene expression profile changes occurring in conjunction with lipopolysaccharide (LPS)-induced proteinuria in mice. <i>Results:</i> We observed dramatic transcriptional reprogramming in glomeruli in response to LPS, representing some 20% of all genes and about 45% of the genes that are normally highly expressed in glomeruli. Bioinformatic analysis revealed significant changes in transcripts encoding proteins involved in the regulation of adherence junctions, actin cytoskeleton and survival in podocytes. In the LPS-treated mice, we observed dysregulation of genes expressed in glomerular endothelial and mesangial cells and in podocytes, there was also a significant decrease in podocyte number. Moreover, collagen α1, α2 (IV) and laminin 10 (laminin α5β1γ1), which are expressed in immature glomeruli, were upregulated in the glomeruli of LPS-treated mice, suggesting remodeling of the glomerular basement membrane and activation of mesangial cells. By superimposing the LPS-induced changes onto GlomNet, a protein-protein interaction network was predicted for podocyte proteins affected by LPS. <i>Conclusions:</i> The detected changes in glomerular gene expression and their involvement in protein interaction networks provide putative markers for early and transient glomerular injury and proteinuria.

<i>背景：</i> 目前学界已对正常肾小球（glomeruli）的全局基因表达模式完成表征，但伴随肾小球疾病发生的基因表达变化仍未得到充分解析。
<i>方法：</i> 本研究针对脂多糖（lipopolysaccharide, LPS）诱导的小鼠蛋白尿模型，绘制了伴随该病理进程的肾小球全局基因表达谱变化图谱。
<i>结果：</i> 研究观察到，小鼠肾小球在响应LPS刺激时发生显著转录重编程，涉及全部基因的约20%，以及正常状态下肾小球高表达基因的约45%。生物信息学分析显示，足细胞（podocytes）中编码参与粘附连接（adherence junctions）调控、肌动蛋白细胞骨架（actin cytoskeleton）调控及细胞存活过程的蛋白的转录本发生显著变化。在LPS处理的小鼠体内，肾小球内皮细胞、系膜细胞及足细胞中表达的基因出现表达失调，同时足细胞数量显著减少。此外，在未成熟肾小球中表达的胶原α1、α2(IV)（collagen α1, α2 (IV)）与层粘连蛋白10（laminin 10, laminin α5β1γ1）在LPS处理小鼠的肾小球中出现上调，提示肾小球基底膜（glomerular basement membrane）发生重塑且系膜细胞被激活。将LPS诱导的基因表达变化叠加至GlomNet后，研究人员成功预测得到受LPS影响的足细胞蛋白的蛋白质相互作用网络。
<i>结论：</i> 本研究检测到的肾小球基因表达变化及其在蛋白质相互作用网络中的参与特征，可为早期一过性肾小球损伤及蛋白尿提供潜在生物标志物。