• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

管状特异性 (P)RR 转基因小鼠的血压升高和可能由于 (P)RR 与替代肾素产物之间的细胞内相互作用导致的致命管状退化。

Blood Pressure Elevation of Tubular Specific (P)RR Transgenic Mice and Lethal Tubular Degeneration due to Possible Intracellular Interactions between (P)RR and Alternative Renin Products.

机构信息

Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan.

Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.

出版信息

Int J Mol Sci. 2021 Dec 28;23(1):302. doi: 10.3390/ijms23010302.

DOI:10.3390/ijms23010302
PMID:35008728
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8745386/
Abstract

The prorenin/renin receptor ((P)RR) is a multifunctional protein that is widely distributed in various organs. Despite intensive research for more than 20 years, this receptor has not been fully characterized. In this study, we generated mice overexpressing the tubular epithelial (P)RR gene ((P)RR-TG mice) to test the previously reported functional role of (P)RR by Ramkumar et al. in 2015 using tubular specific (P)RR KO mice. (P)RR-TG mice were maintained and analyzed in individual metabolic cages and were administered angiotensin II blocker (ARB), direct renin inhibitor (DRI), and bafilomycin, that is, vacuolar ATPase (V-ATPase) antagonist. (P)RR-TG mice were hypertensive and had alkalized urine with lower osmolality and Na excretion. ARB and DRI, but not bafilomycin, concurrently decreased blood pressure. Bafilomycin acidized urine of (P)RR-TG mice, or equivalently this phenomenon restored the effect of overexpressed transgene, suggesting that (P)RR functioned as a V-ATPase in renal tubules. Afterall, (P)RR-TG mice were mated with alternative renin transgenic mice (ARen2-TG), which we identified as intracellular renin previously, to generate double transgenic mice (DT-TG). Lethal renal tubular damage was observed in DT-TG mice, suggesting that intracellular renin may be a ligand for (P)RR in tubules. In summary, (P)RR did not substantially affect the tissue renin-angiotensin system (RAS) in our model of tubular specific (P)RR gene over-expression, but alternative intracellular renin may be involved in (P)RR signaling in addition to conventional V-ATPase function. Further investigations are warranted.

摘要

原肾素/肾素受体 ((P)RR) 是一种多功能蛋白，广泛分布于各种器官。尽管经过 20 多年的深入研究，该受体仍未被充分表征。在这项研究中，我们生成了过表达管状上皮 ((P)RR) 基因的小鼠 ((P)RR-TG 小鼠)，以测试 Ramkumar 等人在 2015 年使用管状特异性 ((P)RR) KO 小鼠报道的 (P)RR 的功能作用。((P)RR-TG 小鼠在单独的代谢笼中维持和分析，并给予血管紧张素 II 阻滞剂 (ARB)、直接肾素抑制剂 (DRI) 和巴弗洛霉素，即液泡型 ATP 酶 (V-ATPase) 拮抗剂。(P)RR-TG 小鼠患有高血压，尿液呈碱性，渗透压和钠排泄降低。ARB 和 DRI，但不是巴弗洛霉素，同时降低血压。巴弗洛霉素酸化 (P)RR-TG 小鼠的尿液，或者等效地恢复过表达转基因的作用，表明 (P)RR 在肾小管中作为 V-ATPase 发挥作用。毕竟，(P)RR-TG 小鼠与替代肾素转基因小鼠 (ARen2-TG) 交配，我们之前将其鉴定为细胞内肾素，以生成双转基因小鼠 (DT-TG)。在 DT-TG 小鼠中观察到致命的肾小管损伤，表明细胞内肾素可能是小管中 (P)RR 的配体。总之，在我们的管状特异性 ((P)RR) 基因过表达模型中，(P)RR 并没有显著影响组织肾素-血管紧张素系统 (RAS)，但替代的细胞内肾素可能除了传统的 V-ATPase 功能外，还参与 (P)RR 信号传导。需要进一步的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/861b4a2eda89/ijms-23-00302-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/c43d22a31a43/ijms-23-00302-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/8340b828670e/ijms-23-00302-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/34c6f6989728/ijms-23-00302-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/b9dcc542ee7f/ijms-23-00302-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/47a489753464/ijms-23-00302-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/d365a0487590/ijms-23-00302-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/a6ca57182af5/ijms-23-00302-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/11e8af9b3548/ijms-23-00302-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/a079a8060fe8/ijms-23-00302-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/a77942a2473b/ijms-23-00302-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/814cb8ead55d/ijms-23-00302-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/861b4a2eda89/ijms-23-00302-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/c43d22a31a43/ijms-23-00302-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/8340b828670e/ijms-23-00302-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/34c6f6989728/ijms-23-00302-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/b9dcc542ee7f/ijms-23-00302-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/47a489753464/ijms-23-00302-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/d365a0487590/ijms-23-00302-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/a6ca57182af5/ijms-23-00302-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/11e8af9b3548/ijms-23-00302-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/a079a8060fe8/ijms-23-00302-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/a77942a2473b/ijms-23-00302-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/814cb8ead55d/ijms-23-00302-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0acb/8745386/861b4a2eda89/ijms-23-00302-g012.jpg

相似文献

1
Blood Pressure Elevation of Tubular Specific (P)RR Transgenic Mice and Lethal Tubular Degeneration due to Possible Intracellular Interactions between (P)RR and Alternative Renin Products.管状特异性 (P)RR 转基因小鼠的血压升高和可能由于 (P)RR 与替代肾素产物之间的细胞内相互作用导致的致命管状退化。
Int J Mol Sci. 2021 Dec 28;23(1):302. doi: 10.3390/ijms23010302.
2
Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport.肾小管上皮细胞前肾素受体调节血压和钠转运。
Am J Physiol Renal Physiol. 2016 Jul 1;311(1):F186-94. doi: 10.1152/ajprenal.00088.2016. Epub 2016 Apr 6.
3
(Pro)renin receptor is required for prorenin-dependent and -independent regulation of vacuolar H⁺-ATPase activity in MDCK.C11 collecting duct cells.原肾素受体是 MDCK.C11 集合管细胞中原肾素依赖性和非依赖性调控液泡 H ⁺ -ATP 酶活性所必需的。
Am J Physiol Renal Physiol. 2013 Aug 1;305(3):F417-25. doi: 10.1152/ajprenal.00037.2013. Epub 2013 May 22.
4
HRP and prorenin: focus on the (pro)renin receptor and vacuolar H+-ATPase.辣根过氧化物酶与肾素原：聚焦于（前）肾素受体和液泡型H⁺-ATP酶
Front Biosci (Schol Ed). 2011 Jun 1;3(4):1205-15. doi: 10.2741/221.
5
The (pro)renin receptor. A decade of research: what have we learned?(原)肾素受体：十年研究，成果几何？
Pflugers Arch. 2013 Jan;465(1):87-97. doi: 10.1007/s00424-012-1105-z. Epub 2012 Apr 28.
6
Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice.集合管肾素原受体基因敲除可降低血管紧张素II诱导的高血压小鼠的肾功能，增加钠排泄，并减轻肾脏反应。
Am J Physiol Renal Physiol. 2017 Dec 1;313(6):F1243-F1253. doi: 10.1152/ajprenal.00152.2017. Epub 2017 Aug 16.
7
The (Pro)renin receptor: site-specific and functional linkage to the vacuolar H+-ATPase in the kidney.（前）肾素受体：与肾脏液泡H⁺-ATP酶的位点特异性及功能联系
Hypertension. 2009 Aug;54(2):261-9. doi: 10.1161/HYPERTENSIONAHA.109.128645. Epub 2009 Jun 22.
8
The Role of the (Pro)renin Receptor in Hypertensive Disease.（前）肾素受体在高血压疾病中的作用。
Am J Hypertens. 2015 Oct;28(10):1187-96. doi: 10.1093/ajh/hpv045. Epub 2015 Apr 18.
9
Cardiac function and architecture are maintained in a model of cardiorestricted overexpression of the prorenin-renin receptor.在肾素原-肾素受体心脏限制性过表达模型中，心脏功能和结构得以维持。
PLoS One. 2014 Feb 25;9(2):e89929. doi: 10.1371/journal.pone.0089929. eCollection 2014.
10
Urinary soluble (pro)renin receptor excretion is associated with urine pH in humans.尿可溶性（pro）肾素受体排泄与人类尿液 pH 值有关。
PLoS One. 2021 Jul 26;16(7):e0254688. doi: 10.1371/journal.pone.0254688. eCollection 2021.

引用本文的文献

1
Development of CAR-T cell therapy for NF1/SWN-related nerve sheath tumor treatment.用于治疗神经纤维瘤病1型/施万素相关神经鞘瘤的嵌合抗原受体T细胞疗法的开发。
Acta Neuropathol Commun. 2025 Mar 1;13(1):45. doi: 10.1186/s40478-025-01965-6.
2
Functional Roles of Furin in Cardio-Cerebrovascular Diseases.弗林蛋白酶在心血管疾病中的功能作用
ACS Pharmacol Transl Sci. 2024 Feb 7;7(3):570-585. doi: 10.1021/acsptsci.3c00325. eCollection 2024 Mar 8.
3
Correlation between glycated hemoglobin A1c, urinary microalbumin, urinary creatinine, β2 microglobulin, retinol binding protein and diabetic retinopathy.

本文引用的文献

1
Functions of the (pro)renin receptor (Atp6ap2) at molecular and system levels: pathological implications in hypertension, renal and brain development, inflammation, and fibrosis.（前）肾素受体（Atp6ap2）在分子和系统水平上的功能：在高血压、肾脏和脑发育、炎症和纤维化中的病理意义。
Pharmacol Res. 2021 Nov;173:105922. doi: 10.1016/j.phrs.2021.105922. Epub 2021 Oct 2.
2
The (pro)renin receptor (ATP6ap2) facilitates receptor-mediated endocytosis and lysosomal function in the renal proximal tubule.（前）肾素受体（ATP6ap2）促进了肾近端小管中受体介导的内吞作用和溶酶体功能。
Pflugers Arch. 2021 Aug;473(8):1229-1246. doi: 10.1007/s00424-021-02598-z. Epub 2021 Jul 6.
3
糖化血红蛋白A1c、尿微量白蛋白、尿肌酐、β2微球蛋白、视黄醇结合蛋白与糖尿病视网膜病变之间的相关性。
World J Diabetes. 2023 Jul 15;14(7):1103-1111. doi: 10.4239/wjd.v14.i7.1103.
4
(Pro)Renin Receptor Decoy Peptide PRO20 Protects against Oxidative Renal Damage Induced by Advanced Oxidation Protein Products.（前）肾素受体诱饵肽 PRO20 可预防晚期氧化蛋白产物引起的氧化肾损伤。
Molecules. 2023 Mar 28;28(7):3017. doi: 10.3390/molecules28073017.
5
How to select the lowest instrumented vertebra in NF-1 non-dystrophic scoliosis.如何选择1型神经纤维瘤病非营养不良性脊柱侧凸中最下固定椎。
Eur Spine J. 2023 Apr;32(4):1153-1160. doi: 10.1007/s00586-023-07600-z. Epub 2023 Feb 21.
Megalin: A Novel Endocytic Receptor for Prorenin and Renin.
巨胞饮受体：原肾素和肾素的一种新型内吞受体。
Hypertension. 2020 May;75(5):1242-1250. doi: 10.1161/HYPERTENSIONAHA.120.14845. Epub 2020 Mar 23.
4
The (pro)renin receptor and its interaction partners.（前）肾素受体及其相互作用伙伴。
Pflugers Arch. 2017 Oct;469(10):1245-1256. doi: 10.1007/s00424-017-2005-z. Epub 2017 Jun 15.
5
Site-1 protease is required for the generation of soluble (pro)renin receptor.可溶性（前体）肾素受体的生成需要1型位点蛋白酶。
J Biochem. 2017 Apr 1;161(4):369-379. doi: 10.1093/jb/mvw080.
6
Renal Atp6ap2/(Pro)renin Receptor Is Required for Normal Vacuolar H+-ATPase Function but Not for the Renin-Angiotensin System.正常的液泡型H⁺-ATP酶功能需要肾Atp6ap2/（前）肾素受体，但肾素-血管紧张素系统则不需要。
J Am Soc Nephrol. 2016 Nov;27(11):3320-3330. doi: 10.1681/ASN.2015080915. Epub 2016 Apr 4.
7
Nephron-specific deletion of the prorenin receptor causes a urine concentration defect.肾素原受体在肾单位特异性缺失会导致尿液浓缩功能缺陷。
Am J Physiol Renal Physiol. 2015 Jul 1;309(1):F48-56. doi: 10.1152/ajprenal.00126.2015. Epub 2015 May 20.
8
The Role of the (Pro)renin Receptor in Hypertensive Disease.（前）肾素受体在高血压疾病中的作用。
Am J Hypertens. 2015 Oct;28(10):1187-96. doi: 10.1093/ajh/hpv045. Epub 2015 Apr 18.
9
Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice.（pro）肾素受体表达增加不会导致小鼠高血压或心脏和肾脏纤维化。
Lab Invest. 2014 Aug;94(8):863-72. doi: 10.1038/labinvest.2014.83. Epub 2014 Jul 21.
10
Identification of bona fide alternative renin transcripts expressed along cortical tubules and potential roles in promoting insulin resistance in vivo without significant plasma renin activity elevation.鉴定沿皮质小管表达的真正替代肾素转录本，并研究其在体内促进胰岛素抵抗的潜在作用，而不会显著升高血浆肾素活性。
Hypertension. 2014 Jul;64(1):125-33. doi: 10.1161/HYPERTENSIONAHA.114.03394. Epub 2014 Apr 28.