Comprehensively characterizing cellular changes and the expression of THSD7A and PLA2R1 under multiple in vitro models of podocyte injury
Comprehensively characterizing cellular changes and the expression of THSD7A and PLA2R1 under multiple in vitro models of podocyte injury
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全面表征多种体外足细胞损伤模型下的细胞变化以及THSD7A和PLA2R1的表达
DOI：
10.1002/cbf.3719
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发表时间：
2022-06
影响因子：
3.6
通讯作者：
Renfang Mao
中科院分区：
文献类型：
--
作者：
Rong Zhang;Yu Shi;Yang Lu;Yuanyuan Wu;Miaomiao Chen;Yihui Fan;Li Yuan;Renfang Mao
足细胞独特的形态和基因表达对肾脏功能至关重要，其异常可导致糖尿病肾病和膜性肾病等肾脏病变。体外培养的足细胞是剖析肾病相关足细胞损伤分子机制的有价值的工具，然而，这些模型从未被全面比较过。在此，我们综合比较了五种常用的体外模型的形态、细胞骨架、细胞黏附、细胞铺展、细胞迁移和脂质代谢，这些模型包括脂多糖(LPS)、嘌呤霉素氨基核苷(PAN)、阿霉素(Dox)、高糖和去糖。我们的结果表明，所有刺激都显著下调了人和小鼠足细胞中突触素的表达。所有刺激都会影响足细胞的形态，但表现出不同的强度和表型。一般来说，这五种刺激可以减少细胞黏附、细胞扩散和细胞迁移，但对人和小鼠足细胞的影响略有不同。人类足细胞表现出丰富的戊糖磷酸途径基因的高表达。DOX和PAN处理对脂质代谢基因表达的影响较大，而其他三种刺激作用较小。在特定细胞中，磷脂酶A2受体(PLA2R1)和含结构域蛋白7A(THSD7A)的表达呈现相反的趋势。刺激可以显著影响PLA2R1和THSD7A的表达。抑制超级增强子降低PLA2R1和THSD7A的表达，而抑制ERK增强它们的表达。我们的结果显示了五种常用的体外足细胞损伤模型的不同反应以及PLA2R1和THSD7A的动态表达，这为选择合适的足细胞损伤模型提供了新的信息。
The unique morphology and gene expression of podocytes are critical for kidney function, and their abnormalities lead to nephropathies such as diabetic nephropathy and membranous nephropathy. Podocytes cultured in vitro are valuable tools to dissect the molecular mechanism of podocyte injury relative to nephropathy, however, these models have never been comprehensively compared. Here, we comprehensively compared the morphology, cytoskeleton, cell adhesion, cell spreading, cell migration, and lipid metabolism under five commonly used in vitro models including lipopolysaccharide (LPS), puromycin aminonucleoside (PAN), doxorubicin (Dox), high glucose, and glucose deprivation. Our results indicate that all stimulations significantly downregulate the expression of synaptopodin both in human and mouse podocytes. All stimulations affect podocyte morphology but show different intensity and phenotypes. In general, the five stimulations reduce cell adhesion, cell spreading, and cell migration, but the effect in human and mouse podocytes is slightly different. Human podocytes show high expression of genes enriched in the pentose phosphate pathway. Dox and PAN treatment show a strong effect on gene expression in lipid metabolism, while the other three stimulations show minimal effect. The expression of phospholipase A2 receptor (PLA2R1) and type-1 domain-containing protein 7 A (THSD7A) show opposite trends in given cells. Stimulations can dramatically affect the expression of PLA2R1 and THSD7A. Inhibition of super-enhancers reduces PLA2R1 and THSD7A expression, but ERK inhibition enhances their expression. Our results demonstrate distinctive responses in five commonly used in vitro podocyte injury models and the dynamic expression of PLA2R1 and THSD7A, which supply novel information to select suitable podocyte injury models.
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影响因子：
7.5
作者：
Svitkina TM
通讯作者：
Svitkina TM
DOI：
--
发表时间：
1970-11
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
M. Arakawa
通讯作者：
M. Arakawa
足细胞GTP酶调节肾脏过滤器动力学。
影响因子：
19.6
作者：
通讯作者：
--
DOI：
10.1016/j.cub.2021.03.031
发表时间：
2021-05-24
期刊：
Current biology : CB
影响因子：
--
作者：
Clarke DN;Martin AC
通讯作者：
Martin AC
DOI：
10.2353/ajpath.2007.070075
发表时间：
2007-08
期刊：
The American journal of pathology
影响因子：
--
作者：
Etsuko Yanagida-Asanuma;K. Asanuma;Kwanghee Kim;M. Donnelly;Hoon Young Choi;Jae Hyung Chang;S. Suetsugu;Y. Tomino;T. Takenawa;C. Faul;P. Mundel
通讯作者：
Etsuko Yanagida-Asanuma;K. Asanuma;Kwanghee Kim;M. Donnelly;Hoon Young Choi;Jae Hyung Chang;S. Suetsugu;Y. Tomino;T. Takenawa;C. Faul;P. Mundel