ArticleJournal of the renin-angiotensin-aldosterone system : JRAAS2016
Overexpression of angiotensinogen downregulates aquaporin 1 expression via modulation of Nrf2-HO-1 pathway in renal proximal tubular cells of transgenic mice.
Article in Journal of the renin-angiotensin-aldosterone system : JRAAS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 9 citations in OpenAlex.
- Effects of a high-salt diet on MAP and expression levels of renal ENaCs and aquaporins in SHR.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Preexisting hypertension and pregnancy-induced hypertension reveal molecular differences in placental proteome in rodents.Physiological genomics · 2021Article
- Angiotensin II up-regulates sodium-glucose co-transporter 2 expression and SGLT2 inhibitor attenuates Ang II-induced hypertensive renal injury in mice.Clinical science (London, England : 1979) · 2021Article
- Effect of fish oil and telmisartan on dehydroepiandrosterone-induced polycystic ovarian syndrome in rats: The role of oxidative stress, transforming growth factor beta-1, and nuclear factor kappa B.Food science & nutrition · 2020Article
- Aldosterone promotes renal interstitial fibrosis via the AIF‑1/AKT/mTOR signaling pathway.Molecular medicine reports · 2019Article
- Activation of the Human Angiotensin-(1-12)-Chymase Pathway in Rats With Human Angiotensinogen Gene Transcripts.Frontiers in cardiovascular medicine · 2019Article
- Aquaporin 11-Dependent Inhibition of Proliferation by Deuterium Oxide in Activated Hepatic Stellate Cells.Molecules (Basel, Switzerland) · 2018Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
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Abstract
introductionWe aimed to examine the regulation of aquaporin 1 expression in an angiotensinogen transgenic mouse model, focusing on underlying mechanisms.
methodsMale transgenic mice overexpressing rat angiotensinogen in their renal proximal tubular cells (RPTCs) and rat immortalised RPTCs stably transfected with rat angiotensinogen cDNA were used.
resultsAngiotensinogen-transgenic mice developed hypertension and nephropathy, changes that were either partially or completely attenuated by treatment with losartan or dual renin-angiotensin system blockade (losartan and perindopril), respectively, while hydralazine prevented hypertension but not nephropathy. Decreased expression of aquaporin 1 and heme oxygenase-1 and increased expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and sodium-hydrogen exchanger 3 were observed in RPTCs of angiotensinogen-transgenic mice and in angiotensinogen-transfected immortalised RPTCs. These parameters were normalised by dual renin-angiotensin system blockade. Both in vivo and in vitro studies identified a novel mechanism in which angiotensinogen overexpression in RPTCs enhances the cytosolic accumulation of Nrf2 via the phosphorylation of pGSK3β Y216. Consequently, lower intranuclear Nrf2 levels are less efficient to trigger heme oxygenase-1 expression as a defence mechanism, which subsequently diminishes aquaporin 1 expression in RPTCs.
conclusionsAngiotensinogen-mediated downregulation of aquaporin 1 and Nrf2 signalling may play an important role in intrarenal renin-angiotensin system-induced hypertension and kidney injury.
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