MyD88 deficiency in podocytes does not change the outcome in experimental glomerulonephritis.. MyD88 deficiency in podocytes does not change the outcome in experimental glomerulonephritis.

Podocytes, together with glomerular endothelial cells, form the kidney filtration barrier. Loss of podocyte function leads to proteinuria and end-stage renal disease. Podocytes are damaged by various diseases. How they respond to damage-associated molecular patterns is however incompletely understood. MyD88 is the central adaptor protein downstream of Toll-like receptor (TLR) / interleukin-1 (IL-1) signaling and key to the initiation of inflammatory responses. Overall design: Here, we challenged WT and podocyte-specific MyD88 knockout mice (MyD88pko) with experimental glomerulonephritis (GN), nephrotoxic nephritis (NTN). Proteinuria, blood urea nitrogen (BUN) and kidney histology were used as read-outs. Podocyte ultrastructure was imaged by STED and infiltrating cells were quantified by FACS. Transcriptomic changes in podocytes of MyD88pko and WT littermate controls were analyzed under healthy and diseased conditions by bulk RNA-seq.

足细胞（podocytes）与肾小球内皮细胞（glomerular endothelial cells）共同构成肾脏滤过屏障。足细胞功能丧失可引发蛋白尿与终末期肾病。多种疾病均可损伤足细胞，但目前人们对足细胞响应损伤相关分子模式的具体机制仍不完全明晰。髓系分化因子88（MyD88）是Toll样受体（TLR）/白细胞介素-1（IL-1）信号通路下游的核心接头蛋白，亦是炎症反应启动的关键调控因子。
总体设计：本研究分别使用实验性肾小球肾炎（GN）与肾毒性肾炎（NTN）对野生型（WT）及足细胞特异性髓系分化因子88敲除小鼠（MyD88pko）进行造模。以蛋白尿、血尿素氮（BUN）及肾脏组织学特征作为核心检测指标。通过受激辐射损耗显微镜（STED）成像观察足细胞超微结构，借助荧光激活细胞分选术（FACS）定量肾脏浸润细胞。分别在健康与患病状态下，通过批量RNA测序（bulk RNA-seq）分析MyD88pko小鼠及其野生型同窝对照小鼠的足细胞转录组变化。