Suppr超能文献

嘌呤霉素氨基核苷诱导的足细胞损伤可被 Smad3 抑制剂 SIS3 改善。

Puromycin aminonucleoside-induced podocyte injury is ameliorated by the Smad3 inhibitor SIS3.

机构信息

Pediatric Department, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing, China.

Pediatric Department, Peking University First Hospital, Beijing, China.

出版信息

FEBS Open Bio. 2020 Aug;10(8):1601-1611. doi: 10.1002/2211-5463.12916. Epub 2020 Jul 7.

Abstract

Smad3 signaling and transgelin expression are often activated during puromycin aminonucleoside (PAN)-induced podocyte injury. Here, we investigated whether the Smad3 inhibitor SIS3 can ameliorate damage to injured podocytes. A model of PAN-induced podocyte injury was constructed using the MPC5 cell line. The effects of SIS3 on the expression of the podocyte cytoskeletal proteins transgelin, p15 , phosphor-smad3, phosphor-JAK/stat3, the apoptotic marker cleaved caspase 3, and c-myc were investigated using western blot. The distribution of F-actin in PAN-induced podocyte injury was observed under an immunofluorescence microscope. PAN-induced podocyte injury altered the distribution of F-actin and transgelin, and colocalization of these two proteins was observed. Transgelin expression and Smad3 phosphorylation were increased in the MPC5 cell line with prolonged PAN treatment. In addition, c-myc expression, p15 , and JAK phosphorylation were all increased after treatment with PAN. Treatment with the Smad3 inhibitor SIS3 reversed these phenomena and protected against PAN-induced podocyte injury. Moreover, stimulating podocytes directly with TGFβ-1 also led to enhanced expression of transgelin or phosphor-JAK/stat3, and this could be inhibited by SIS3. In conclusion, transgelin expression was induced through the Smad3 signaling pathway during PAN-induced podocyte injury, and the resulting abnormal distribution of F-actin and the enhanced expression of transgelin could be reversed by blockade of this pathway.

摘要

Smad3 信号转导和转谷氨酰胺酶表达在嘌呤霉素氨基核苷 (PAN) 诱导的足细胞损伤中常常被激活。在这里,我们研究了 Smad3 抑制剂 SIS3 是否可以改善受损足细胞的损伤。使用 MPC5 细胞系构建了 PAN 诱导的足细胞损伤模型。使用 Western blot 检测 SIS3 对足细胞细胞骨架蛋白转谷氨酰胺酶、p15、磷酸化 Smad3、磷酸化 JAK/stat3、凋亡标志物 cleaved caspase 3 和 c-myc 的表达的影响。在免疫荧光显微镜下观察 PAN 诱导的足细胞损伤中 F-肌动蛋白的分布。PAN 诱导的足细胞损伤改变了 F-肌动蛋白和转谷氨酰胺酶的分布,并观察到这两种蛋白的共定位。随着 PAN 处理时间的延长,MPC5 细胞系中转谷氨酰胺酶表达和 Smad3 磷酸化增加。此外,PAN 处理后 c-myc 表达、p15 和 JAK 磷酸化均增加。Smad3 抑制剂 SIS3 处理可逆转这些现象并保护足细胞免受 PAN 诱导的损伤。此外,直接刺激足细胞也会导致转谷氨酰胺酶或磷酸化 JAK/stat3 的表达增强,而 SIS3 可以抑制这种增强。总之,在 PAN 诱导的足细胞损伤中,转谷氨酰胺酶表达是通过 Smad3 信号通路诱导的,该通路的阻断可以逆转由此导致的 F-肌动蛋白异常分布和转谷氨酰胺酶表达增强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1764/7396432/baf9cd549fa7/FEB4-10-1601-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验