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Bicellular Localization of Tricellular Junctional Protein Angulin-3/ILDR2 Allows Detection of Podocyte Injury
The American Journal of Pathology ( IF 4.7 ) Pub Date : 2024-02-02 , DOI: 10.1016/j.ajpath.2024.01.008
Atsuko Y Higashi 1 , Akira C Saito 2 , Tomohito Higashi 2 , Kyoko Furuse 3 , Mikio Furuse 4 , Hideki Chiba 2 , Junichiro J Kazama 1
The American Journal of Pathology ( IF 4.7 ) Pub Date : 2024-02-02 , DOI: 10.1016/j.ajpath.2024.01.008
Atsuko Y Higashi 1 , Akira C Saito 2 , Tomohito Higashi 2 , Kyoko Furuse 3 , Mikio Furuse 4 , Hideki Chiba 2 , Junichiro J Kazama 1
Affiliation
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Podocytes serve as part of the renal filtration unit with slit diaphragms. Although the structure of slit diaphragms between two cells is well characterized, how the tricellular contact of podocytes is organized and how it changes in injured podocytes remains unknown. This study focused on a tricellular junction protein, angulin-3, and its localization in healthy podocytes, in developmental stages, and in pathologic conditions, using a newly established monoclonal antibody. Angulin-3 was confined at tricellular junctions of primordial podocytes, then transiently localized at bicellular junctions as foot process interdigitation developed and the intercellular junctions rearranged into slit diaphragm, and eventually distributed in a sparse punctate pattern on the foot processes of adult podocytes. In the rodent podocyte injury models, angulin-3 showed bicellular localization between the foot processes, and the localization turned from punctate to dashed linear pattern along the effaced foot processes with the progression of podocyte injury. Angulin-3 also accumulated between foot processes in a linear pattern in kidney biopsy samples of human nephrotic syndrome. Additionally, the line length of angulin-3 staining signal correlated with risk of relapse under glucocorticoid therapy in patients with minimal change nephrotic syndrome. This study proposes an image program to score the linearity of the accumulation pattern of angulin-3 to evaluate the relapse risk of patients with minimal change nephrotic syndrome.
中文翻译:
三细胞连接蛋白 Angulin-3/ILDR2 的双细胞定位可检测足细胞损伤
足细胞是具有狭缝隔膜的肾过滤单元的一部分。尽管两个细胞之间的狭缝隔膜的结构已得到很好的表征,但足细胞的三细胞接触是如何组织的以及它在受伤的足细胞中如何变化仍然未知。本研究使用新建立的单克隆抗体,重点关注三细胞连接蛋白 angulin-3 及其在健康足细胞、发育阶段和病理条件下的定位。 Angulin-3 被限制在原始足细胞的三细胞连接处,然后随着足突叉指的发展和细胞间连接重新排列成裂隙隔膜而短暂地定位在双细胞连接处,并最终以稀疏的点状图案分布在成年足细胞的足突上。在啮齿动物足细胞损伤模型中,angulin-3在足突之间表现出双细胞定位,并且随着足细胞损伤的进展,沿着消失的足突定位从点状转变为虚线状模式。在人类肾病综合征的肾活检样本中,Angulin-3 也在足突之间以线性模式积累。此外,angulin-3染色信号的线长度与微小病变肾病综合征患者在糖皮质激素治疗下复发的风险相关。本研究提出了一种图像程序,对 angulin-3 积累模式的线性进行评分,以评估微小病变肾病综合征患者的复发风险。
更新日期:2024-02-02
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
三细胞连接蛋白 Angulin-3/ILDR2 的双细胞定位可检测足细胞损伤
足细胞是具有狭缝隔膜的肾过滤单元的一部分。尽管两个细胞之间的狭缝隔膜的结构已得到很好的表征,但足细胞的三细胞接触是如何组织的以及它在受伤的足细胞中如何变化仍然未知。本研究使用新建立的单克隆抗体,重点关注三细胞连接蛋白 angulin-3 及其在健康足细胞、发育阶段和病理条件下的定位。 Angulin-3 被限制在原始足细胞的三细胞连接处,然后随着足突叉指的发展和细胞间连接重新排列成裂隙隔膜而短暂地定位在双细胞连接处,并最终以稀疏的点状图案分布在成年足细胞的足突上。在啮齿动物足细胞损伤模型中,angulin-3在足突之间表现出双细胞定位,并且随着足细胞损伤的进展,沿着消失的足突定位从点状转变为虚线状模式。在人类肾病综合征的肾活检样本中,Angulin-3 也在足突之间以线性模式积累。此外,angulin-3染色信号的线长度与微小病变肾病综合征患者在糖皮质激素治疗下复发的风险相关。本研究提出了一种图像程序,对 angulin-3 积累模式的线性进行评分,以评估微小病变肾病综合征患者的复发风险。