ArticleThe Journal of biological chemistry2010
Intrarenal renin angiotensin system revisited: role of megalin-dependent endocytosis along the proximal nephron.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 142 citations in OpenAlex.
- mTORC1-signaling switches megalin function from endocytosis to cell cycle progression.Cellular and molecular life sciences : CMLS · 2026Article
- Effects and regulation of ACE2 and TMPRSS2 abundance in healthy humans and in patients with SARS-CoV-2.Biochemical Society transactions · 2025Article
- Augmented Intrarenal and Urinary Angiotensinogen in Diabetic Nephropathy: The Role of Isoflavones.International journal of molecular sciences · 2025Review
- Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western Diet.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Renal Proximal Tubule Cell-specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed Western Diet.bioRxiv : the preprint server for biology · 2024Article
- Angiotensinogen as a Therapeutic Target for Cardiovascular and Metabolic Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Parental recovered acute kidney injury causes prenatal renal dysfunction and fetal growth restriction with sexually dimorphic implications for adult offspring.Frontiers in physiology · 2024Article
- Internalization of Angiotensin-(1-12) in Adult Retinal Pigment Epithelial-19 Cells.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023Article
- Article
- Urinary Angiotensinogen in Patients With Type 1 Diabetes With Microalbuminuria: Gender Differences and Effect of Intensive Insulin Therapy.Kidney international reports · 2022Article
- Hepatic and proximal tubule angiotensinogen play distinct roles in kidney dysfunction, glomerular and tubular injury, and fibrosis progression.American journal of physiology. Renal physiology · 2022Article
- Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.Pharmacological reviews · 2022Review
- Angiotensinogen uptake and stimulation of oxidative stress in human pigment retinal epithelial cells.Peptides · 2022Article
- Role and Mechanism of the Renin-Angiotensin-Aldosterone System in the Onset and Development of Cardiorenal Syndrome.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2022Review
- 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.International journal of molecular sciences · 2021Article
- The evolving complexity of the collecting duct renin-angiotensin system in hypertension.Nature reviews. Nephrology · 2021Review
- MicroRNA-133a-Dependent Inhibition of Proximal Tubule Angiotensinogen by Renal TNF (Tumor Necrosis Factor).Hypertension (Dallas, Tex. : 1979) · 2020Article
- Megalin: a Novel Determinant of Renin-Angiotensin System Activity in the Kidney?Current hypertension reports · 2020Review
- CG200745, a Novel HDAC Inhibitor, Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome.International journal of molecular sciences · 2020Article
- Megalin: A bridge connecting kidney, the renin-angiotensin system, and atherosclerosis.Pharmacological research · 2020Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The existence of a local renin angiotensin system (RAS) of the kidney has been established. Angiotensinogen (AGT), renin, angiotensin-converting enzyme (ACE), angiotensin receptors, and high concentrations of luminal angiotensin II have been found in the proximal tubule. Although functional data have documented the relevance of a local RAS, the dualism between biosynthesis and endocytotic uptake of its components and their cellular processing has been incompletely understood. To resolve this, we have selectively analyzed their distribution, endocytosis, transcytosis, and biosynthesis in the proximal tubule. The presence of immunoreactive AGT, restricted to the early proximal tubule, was due to its retrieval from the ultrafiltrate and storage in endosomal and lysosomal compartments. Cellular uptake was demonstrated by autoradiography of radiolabeled AGT and depended on intact endocytosis. AGT was identified as a ligand of the multiple ligand-binding repeats of megalin. AGT biosynthesis was restricted to the proximal straight tubule, revealing substantial AGT mRNA expression. Transgenic AGT overexpression under the control of an endogenous promoter was also restricted to the late proximal tubule. Proximal handling of renin largely followed the patterns of AGT, whereas its local biosynthesis was not significant. Transcytotic transport of AGT in a proximal cell line revealed a 5% recovery rate after 1 h. ACE was expressed along late proximal brush-border membrane, whereas ACE2 was present along the entire segment. Surface expression of ACE and ACE2 differed as a function of endocytosis. Our data on the localization and cellular processing of RAS components provide new aspects of the functional concept of a "self-contained" renal RAS.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.