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肾小管细胞中Pten的缺失通过上调水通道蛋白2导致水潴留。

Loss of Pten in Renal Tubular Cells Leads to Water Retention by Upregulating AQP2.

作者信息

Sun Zhuo, Shao Xiaotong, Wu Haotian, Zhao Yaxian, Cao Yidan, Li Danhua, Sun Ying, Wang Qingling

机构信息

Department of Pathology, Laboratory of Clinical and Experimental Pathology, Xuzhou Medical University, Xuzhou, China.

Department of Pathology, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, China.

出版信息

Kidney Dis (Basel). 2022 Nov 29;9(1):58-71. doi: 10.1159/000528010. eCollection 2023 Jan.

DOI:10.1159/000528010
PMID:36756085
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9900467/
Abstract

INTRODUCTION

Phosphatase and tensin (PTEN) is a multifunctional gene associated with the normal development and physiological function of various tissues including the kidney. However, its role in renal tubular reabsorption function has not been well elucidated.

METHODS

We generated a renal tubule-specific knockout mouse model by crossing mice with transgenic mice, evaluated the effect of loss on renal tubular function, and investigated the underlying mechanisms.

RESULTS

loss resulted in abnormal renal structure and function and water retention in multiple organs. Our results also demonstrated that aquaporin-2 (AQP2), an important water channel protein, was upregulated and concentrated on the apical plasma membrane of collecting duct cells, which could be responsible for the impaired water balance in loss mice. The regulation of loss on AQP2 was mediated by protein kinase B (AKT) activation.

CONCLUSIONS

Our results reveal a connection between gene inactivation and water retention, suggesting the importance of PTEN in normal kidney development and function.

摘要

引言

磷酸酶和张力蛋白(PTEN)是一种多功能基因,与包括肾脏在内的各种组织的正常发育和生理功能相关。然而,其在肾小管重吸收功能中的作用尚未得到充分阐明。

方法

我们通过将小鼠与转基因小鼠杂交,构建了肾小管特异性敲除小鼠模型,评估了PTEN缺失对肾小管功能的影响,并探究了其潜在机制。

结果

PTEN缺失导致肾脏结构和功能异常以及多个器官积水。我们的结果还表明,水通道蛋白2(AQP2),一种重要的水通道蛋白,在集合管细胞的顶端质膜上上调并聚集,这可能是PTEN缺失小鼠水平衡受损的原因。PTEN缺失对AQP2的调节是由蛋白激酶B(AKT)激活介导的。

结论

我们的结果揭示了PTEN基因失活与积水之间的联系,表明PTEN在正常肾脏发育和功能中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/dee0b2330743/kdd-0009-0058-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/5b090b9b4ed4/kdd-0009-0058-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/41b39fe09a32/kdd-0009-0058-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/0d395ee7d212/kdd-0009-0058-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/1b74db540b96/kdd-0009-0058-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/dee0b2330743/kdd-0009-0058-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/5b090b9b4ed4/kdd-0009-0058-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/41b39fe09a32/kdd-0009-0058-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/0d395ee7d212/kdd-0009-0058-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/1b74db540b96/kdd-0009-0058-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c2a/9900467/dee0b2330743/kdd-0009-0058-g05.jpg

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本文引用的文献

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Serum Level of Polyubiquitinated PTEN and Loss of Kidney Function in American Indians With Type 2 Diabetes.血清多聚泛素化 PTEN 水平与 2 型糖尿病美国印第安人肾功能丧失的关系。
Am J Kidney Dis. 2022 Apr;79(4):497-506. doi: 10.1053/j.ajkd.2021.08.009. Epub 2021 Sep 22.
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PTEN protects kidney against acute kidney injury by alleviating apoptosis and promoting autophagy via regulating HIF1-α and mTOR through PI3K/Akt pathway.PTEN 通过调节 HIF1-α 和 mTOR 通路,通过 PI3K/Akt 途径减轻细胞凋亡并促进自噬,从而保护肾脏免受急性肾损伤。
Exp Cell Res. 2021 Sep 1;406(1):112729. doi: 10.1016/j.yexcr.2021.112729. Epub 2021 Jul 7.
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Genomic profiling in renal cell carcinoma.
肾细胞癌的基因组分析。
Nat Rev Nephrol. 2020 Aug;16(8):435-451. doi: 10.1038/s41581-020-0301-x. Epub 2020 Jun 19.
4
Protein phosphatase Mg /Mn dependent-1A and PTEN deregulation in renal fibrosis: Novel mechanisms and co-dependency of expression.蛋白磷酸酶 Mg/Mn 依赖性 1A 和 PTEN 在肾纤维化中的失调:新的机制和表达的共同依赖性。
FASEB J. 2020 Feb;34(2):2641-2656. doi: 10.1096/fj.201902015RR. Epub 2019 Dec 23.
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PTEN-knockdown disrupts the morphology, growth pattern and function of Nthy-Ori 3-1 cells by downregulating PAX8 expression.PTEN基因敲低通过下调PAX8表达破坏了Nthy-Ori 3-1细胞的形态、生长模式和功能。
Oncol Lett. 2019 Dec;18(6):6732-6740. doi: 10.3892/ol.2019.11028. Epub 2019 Oct 31.
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PTEN improve renal fibrosis in vitro and in vivo through inhibiting FAK/AKT signaling pathway.PTEN通过抑制FAK/AKT信号通路在体外和体内改善肾纤维化。
J Cell Biochem. 2019 Oct;120(10):17887-17897. doi: 10.1002/jcb.29057. Epub 2019 May 29.
7
Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma.PTEN突变在透明细胞肾细胞癌的细胞进程、预后及药物选择中的意义
Front Oncol. 2019 May 8;9:357. doi: 10.3389/fonc.2019.00357. eCollection 2019.
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J Clin Invest. 2019 Mar 1;129(3):1129-1151. doi: 10.1172/JCI121987. Epub 2019 Feb 11.
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Renal collecting duct physiology and pathophysiology .肾集合管生理学与病理生理学
Biochem Cell Biol. 2019 Jun;97(3):234-242. doi: 10.1139/bcb-2018-0192. Epub 2018 Sep 12.
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The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma.癌症基因组图谱:肾细胞癌的全面分子特征
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