ArticleHypertension (Dallas, Tex. : 1979)2012
Genetic variants in Arhgef11 are associated with kidney injury in the Dahl salt-sensitive rat.
Article in Hypertension (Dallas, Tex. : 1979), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 36 citations in OpenAlex.
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- Systematic prioritization of potential therapeutic targets for glomerulonephritis using multi-omics Mendelian randomization.PLoS computational biology · 2026Article
- Beyond Blood Pressure: Emerging Pathways and Precision Approaches in Hypertension-Induced Kidney Damage.International journal of molecular sciences · 2025Review
- Article
- Brown-Norway chromosome 1 mitigates the upregulation of proinflammatory pathways in mTAL cells and subsequent age-related CKD in Dahl SS/JrHsdMcwi rats.American journal of physiology. Renal physiology · 2023Article
- Six Decades of History of Hypertension Research at the University of Toledo: Highlighting Pioneering Contributions in Biochemistry, Genetics, and Host-Microbiota Interactions.Current hypertension reports · 2022Review
- Research on the Mechanism and Prevention of Hypertension Caused by Apatinib Through the RhoA/ROCK Signaling Pathway in a Mouse Model of Gastric Cancer.Frontiers in cardiovascular medicine · 2022Article
- Cooperation of augmented calcium sensitization and increased calcium entry contributes to high blood pressure in salt-sensitive Dahl rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Nephron-deficient HSRA rats exhibit renal injury with age but have limited renal damage from streptozotocin-induced hyperglycemia.American journal of physiology. Renal physiology · 2021Article
- Role of Rho in Salt-Sensitive Hypertension.International journal of molecular sciences · 2021Review
- Sept8/SEPTIN8 involvement in cellular structure and kidney damage is identified by genetic mapping and a novel human tubule hypoxic model.Scientific reports · 2021Article
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Using Genetic and Species Diversity to Tackle Kidney Disease.Trends in genetics : TIG · 2020Review
- Loss ofHypertension (Dallas, Tex. : 1979) · 2020Article
- Temporal Expression and Cellular Localization of PAPPA2 in the Developing Kidney of Rat.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Article
- Will the real Dahl S rat please stand up?American journal of physiology. Renal physiology · 2019Article
- Prevention of the progression of renal injury in diabetic rodent models with preexisting renal disease with chronic endothelin A receptor blockade.American journal of physiology. Renal physiology · 2018Article
- Spontaneous one-kidney rats are more susceptible to develop hypertension by DOCA-NaCl and subsequent kidney injury compared with uninephrectomized rats.American journal of physiology. Renal physiology · 2016Article
- Low Doses of Cisplatin Induce Gene Alterations, Cell Cycle Arrest, and Apoptosis in Human Promyelocytic Leukemia Cells.Biomarker insights · 2016Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
A previous genetic analysis comparing the Dahl salt-sensitive (S) rat with the spontaneously hypertensive rat identified a major locus on chromosome 2 that influences proteinuria in the S rat. In the present study, blood pressure, proteinuria, and renal hemodynamics were evaluated in congenic strains with small segments of the protective spontaneously hypertensive rat genome on the S background. Proteinuria and renal function were significantly improved in the congenic strains compared with the S. The causative locus interval was narrowed to <375 kb on the basis of congenic strains, haplotype data, comparative mapping, and concordance with human genetic studies. Sequencing of the coding region of genes in this region identified 36 single nucleotide polymorphisms (13 nonsynonymous and 23 synonymous). Gene expression profiling indicated that only a few genes exhibited differential expression. Arhgef11, Pear1, and Sh2d2 were identified as important candidate genes that may be linked to kidney injury in the S rat. In particular, Arhgef11 plays an important role in the activation of the Rho-ROCK signaling pathway. Inhibition of this pathway using fasudil resulted in a significant reduction of proteinuria in treated S rats (compared with untreated S). However, no difference was observed between treated or untreated spontaneously hypertensive rat or congenic strains. The homologous region in humans was found to be associated with estimated glomerular filtration rate in the Candidate Gene Association Resource population. In summary, these findings demonstrate that allelic variants in Arhgef11, acting through the Rho-ROCK pathway, could influence kidney injury in the S as well as provide insight into human kidney disease.
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