ArticleAmerican journal of physiology. Renal physiology2014
Mechanisms of AT1a receptor-mediated uptake of angiotensin II by proximal tubule cells: a novel role of the multiligand endocytic receptor megalin.
Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Intratubular, Intracellular, and Mitochondrial Angiotensin II/ATFrontiers in physiology · 2021Review
- The renal antioxidative effect of losartan involves heat shock protein 70 in proximal tubule cells.Cell stress & chaperones · 2020Review
- Evidence for a Physiological Mitochondrial Angiotensin II System in the Kidney Proximal Tubules: Novel Roles of Mitochondrial Ang II/ATHypertension (Dallas, Tex. : 1979) · 2020Article
- Megalin: a Novel Determinant of Renin-Angiotensin System Activity in the Kidney?Current hypertension reports · 2020Review
- The role of lipocalin-2 in age-related macular degeneration (AMD).Cellular and molecular life sciences : CMLS · 2020Review
- Megalin: A bridge connecting kidney, the renin-angiotensin system, and atherosclerosis.Pharmacological research · 2020Review
- Emerging concepts of receptor endocytosis and concurrent intracellular signaling: Mechanisms of guanylyl cyclase/natriuretic peptide receptor-A activation and trafficking.Cellular signalling · 2019Review
- Losartan and Vitamin D Inhibit Colonic Tumor Development in a Conditional Apc-Deleted Mouse Model of Sporadic Colon Cancer.Cancer prevention research (Philadelphia, Pa.) · 2019Article
- The effect of A1 adenosine receptor in diabetic megalin loss with caspase-1/IL18 signaling.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- Megalin mediates plasma membrane to mitochondria cross-talk and regulates mitochondrial metabolism.Cellular and molecular life sciences : CMLS · 2018Article
- Intratubular and intracellular renin-angiotensin system in the kidney: a unifying perspective in blood pressure control.Clinical science (London, England : 1979) · 2018Review
- Immunohistochemical expression of intrarenal renin angiotensin system components in response to tempol in rats fed a high salt diet.World journal of nephrology · 2017Article
- Recent Updates on the Proximal Tubule Renin-Angiotensin System in Angiotensin II-Dependent Hypertension.Current hypertension reports · 2016Review
- Overexpression of angiotensinogen downregulates aquaporin 1 expression via modulation of Nrf2-HO-1 pathway in renal proximal tubular cells of transgenic mice.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2016Article
- Augmentation of angiotensinogen expression in the proximal tubule by intracellular angiotensin II via AT1a/MAPK/NF-кB signaling pathways.American journal of physiology. Renal physiology · 2016Article
- Role of caveolin 1 in AT1a receptor-mediated uptake of angiotensin II in the proximal tubule of the kidney.American journal of physiology. Renal physiology · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The present study tested the hypothesis that the multiligand endocytic receptor megalin is partially involved in the uptake of ANG II and downstream signaling responses in mouse proximal tubule cells (mPCT) by interacting with AT1a receptors. mPCT cells of wild-type (WT) and AT1a receptor-deficient (AT1a-KO) mice were treated with vehicle, the AT1 receptor blocker losartan (10 μM), or a selective megalin small interfering (si) RNA for 48 h. The uptake of fluorescein (FITC)-labeled ANG II (10 nM, 37°C) and downstream signaling responses were analyzed by fluorescence imaging and Western blotting. AT1a receptors and megalin were abundantly expressed in mPCT cells, whereas AT1a receptors were absent in AT1a-KO mPCT cells (P < 0.01). In WT mPCT cells, FITC-ANG II uptake was visualized at 30 min in the cytoplasm and in the nuclei 1 h after exposure. Losartan alone completely blocked the uptake of FITC-ANG II, whereas megalin siRNA inhibited only 30% of the response (P < 0.01). The remaining FITC-ANG II uptake in the presence of megalin siRNA was completely abolished by losartan. ANG II induced threefold increases in phosphorylated MAP kinases ERK1/2 and a onefold increase in phosphorylated sodium and hydrogen exchanger 3 (NHE3) proteins, which were also blocked by losartan and megalin-siRNA. By contrast, losartan and megalin siRNA had no effects on these signaling proteins in AT1a-KO mPCT cells. We conclude that the uptake of ANG II and downstream MAP kinases ERK1/2 and NHE3 signaling responses in mPCT cells are mediated primarily by AT1a receptors. However, megalin may also play a partial role in these responses to ANG II.
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