Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia,The FASEB Journal

当前位置： X-MOL 学术 › FASEB J. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia
The FASEB Journal ( IF 4.4 ) Pub Date : 2023-03-24 , DOI: 10.1096/fj.202201546rr
Ping Wang _{1,

2} , Gangyi Zhu ₁ , Qiaozhen Wu ₃ , Li Shen ₄ , Dan Liu ₄ , Zhiyin Wang ₄ , Weiwan Wang ₁ , Zhiyun Ren ₁ , Yutao Jia ₂ , Mingda Liu ₁ , Ying Xue ₁ , Daxi Ji ₂ , Yali Hu ₄ , Yanting Yu _{1,

2} , Xiaoyan Wang _{1,

2}

Affiliation

The kidney regulates blood pressure through salt/water reabsorption affected by tubular sodium transporters. Expanding our prior research on placental cluster of differentiation 81 (CD81), this study explores the interaction of renal CD81 with sodium transporters in preeclampsia (PE). Effects of renal CD81 with sodium transporters were determined in lipopolysaccharide (LPS)-induced PE rats and immortalized mouse renal distal convoluted tubule cells. Urinary exosomal CD81, sodium potassium 2 chloride cotransporter (NKCC2), and sodium chloride cotransporter (NCC) were measured in PE patients. LPS-PE rats had hypertension from gestational days (GD) 6 to 18 and proteinuria from GD9 to GD18. Urinary CD81 in both groups tented to rise during pregnancy. Renal CD81, not sodium transporters, was higher in LPS-PE than controls on GD14. On GD18, LPS-PE rats exhibited higher CD81 in kidneys and urine exosomes, higher renal total and phosphorylated renal NKCC2 and NCC with elevated mRNAs, and lower ubiquitinated NCC than controls. CD81 was co-immunoprecipitated with NKCC2 or NCC in kidney homogenates and co-immunostained with NKCC2 or NCC in apical membranes of renal tubules. In plasma membrane fractions, LPS-PE rats had greater amounts of CD81, NKCC2, and NCC than controls with enhanced co-immunoprecipitations of CD81 with NKCC2 or NCC. In renal distal convoluted tubule cells, silencing CD81 with siRNA inhibited NCC and prevented LPS-induced NCC elevation. Further, PE patients had higher CD81 in original urines, urine exosomes and higher NKCC2 and NCC in urine exosomes than controls. Thus, the upregulation of renal CD81 on NKCC2 and NCC may contribute to the sustained hypertension observed in LPS-PE model. Urine CD81 with NKCC2 and NCC may be used as biomarkers for PE.

中文翻译：

脂多糖诱导的先兆子痫大鼠肾脏 CD81 与钠钾 2 氯化物协同转运蛋白和氯化钠协同转运蛋白相互作用

肾脏通过受管状钠转运蛋白影响的盐/水重吸收来调节血压。扩大我们之前对胎盘分化簇 81 (CD81) 的研究，本研究探讨了先兆子痫 (PE) 中肾脏 CD81 与钠转运蛋白的相互作用。在脂多糖 (LPS) 诱导的 PE 大鼠和永生化小鼠肾远曲小管细胞中确定了肾 CD81 与钠转运蛋白的作用。在 PE 患者中测量了尿外泌体 CD81、氯化钠钾 2 协同转运蛋白 (NKCC2) 和氯化钠协同转运蛋白 (NCC)。LPS-PE 大鼠从妊娠天数 (GD) 6 到 18 有高血压，从 GD9 到 GD18 有蛋白尿。两组的尿液 CD81 在怀孕期间都有上升趋势。LPS-PE 中的肾 CD81（而非钠转运蛋白）高于 GD14 的对照。在 GD18 上，LPS-PE 大鼠在肾脏和尿液外泌体中表现出更高的 CD81、更高的肾脏总和磷酸化肾脏 NKCC2 和 NCC 以及更高的 mRNA，以及更低的泛素化 NCC。CD81 与肾匀浆中的 NKCC2 或 NCC 共免疫沉淀，并与肾小管顶膜中的 NKCC2 或 NCC 共免疫染色。在质膜组分中，LPS-PE 大鼠的 CD81、NKCC2 和 NCC 数量高于对照组，CD81 与 NKCC2 或 NCC 的免疫共沉淀增强。在肾远曲小管细胞中，用 siRNA 沉默 CD81 可抑制 NCC 并阻止 LPS 诱导的 NCC 升高。此外，与对照组相比，PE 患者的原始尿液、尿液外泌体中的 CD81 更高，尿液外泌体中的 NKCC2 和 NCC 更高。因此，NKCC2 和 NCC 上肾 CD81 的上调可能有助于在 LPS-PE 模型中观察到的持续高血压。尿液 CD81 与 NKCC2 和 NCC 可用作 PE 的生物标志物。

更新日期：2023-03-24

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文