Department of Anatomy and Life Structure and
Laboratory of Morphology and Image Analysis, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
J Am Soc Nephrol. 2019 Jan;30(1):96-108. doi: 10.1681/ASN.2018020139. Epub 2018 Dec 4.
Foot process effacement is one of the pathologic indicators of podocyte injury. However, the morphologic changes associated with it remain unclear.
To clarify the developmental process, we analyzed puromycin nephrotic podocytes reconstructed from serial focused-ion beam/scanning electron microscopy (FIB/SEM) images.
Intact podocytes consisted of four subcellular compartments: cell body, primary process, ridge-like prominence (RLP), and foot process. The RLP, a longitudinal protrusion from the basal surface of the cell body and primary process, served as an adhesive apparatus for the cell body and primary process to attach to the glomerular basement membrane. Foot processes protruded from both sides of the RLP. In puromycin nephrotic podocytes, foot process effacement occurred in two ways: by type-1 retraction, where the foot processes retracted while maintaining their rounded tips; or type-2 retraction, where they narrowed across their entire lengths, tapering toward the tips. Puromycin nephrotic podocytes also exhibited several alterations associated with foot process effacement, such as deformation of the cell body, retraction of RLPs, and cytoplasmic fragmentation. Finally, podocytes were reorganized into a broad, flattened shape.
The three-dimensional reconstruction of podocytes by serial FIB/SEM images revealed the morphologic changes involved in foot process effacement in greater detail than previously described.
足细胞裂孔消失是足细胞损伤的病理指标之一。然而，与之相关的形态变化仍不清楚。
为了阐明这一过程，我们对从小鼠足细胞裂孔消失模型中分离得到的、经连续聚焦离子束/扫描电镜（FIB/SEM）成像重构的足细胞进行了分析。
完整的足细胞由四个亚细胞区室组成：细胞体、初级突起、嵴样隆起（RLP）和足突。RLP 是从细胞体和初级突起的基底面纵向伸出的突起，是将细胞体和初级突起附着到肾小球基底膜的附着装置。足突从 RLP 的两侧伸出。在嘌呤霉素肾病足细胞中，足突裂孔消失有两种方式：1 型回缩，足突回缩但保持圆顶状；2 型回缩，整个足突变窄，向顶端逐渐变细。嘌呤霉素肾病足细胞还表现出与足突裂孔消失相关的几种改变，如细胞体变形、RLP 回缩和细胞质碎片化。最后，足细胞被重新组织成宽阔的扁平形状。
通过连续 FIB/SEM 图像对足细胞进行三维重建，比以前的描述更详细地揭示了足突裂孔消失所涉及的形态变化。
