ArticleInternational journal of molecular sciences2016
Angiotensin II Stimulation of DPP4 Activity Regulates Megalin in the Proximal Tubules.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Effect of DPP-4i inhibitors on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.Lipids in health and disease · 2024Pooled it
- Receptor-mediated endocytosis by Megalin: Exploring its role in ligand interaction and disease mechanisms.Genes & diseases · 2026Review
- The SGLT2i "canagliflozin" and the DPP-4i "sitagliptin" mitigate hypertensive nephropathy in adult male rats by modulating the Ang II/RAGE/Nox4/NLRP3 cascade.Frontiers in physiology · 2026Article
- Unique Role of Proximal Tubule Dipeptidyl Peptidase 4 on Blood Pressure, Renal Sodium Handling, and NaActa physiologica (Oxford, England) · 2025Article
- Association of urinary dipeptidyl peptidase 4 activity with clinical outcomes in people with chronic kidney disease.Scientific reports · 2025Article
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.International journal of molecular sciences · 2024Review
- Bidirectional relation between dipeptidyl peptidase 4 and angiotensin II type I receptor signaling.American journal of physiology. Cell physiology · 2024Article
- Review
- Participation of OCRL1, and APPL1, in the expression, proteolysis, phosphorylation and endosomal trafficking of megalin: Implications for Lowe Syndrome.Frontiers in cell and developmental biology · 2022Article
- An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection.Frontiers in microbiology · 2022Review
- The SARS-CoV-2 receptor and other key components of the Renin-Angiotensin-Aldosterone System related to COVID-19 are expressed in enterocytes in larval zebrafish.Biology open · 2021Article
- DPP4 inhibition mitigates ANG II-mediated kidney immune activation and injury in male mice.American journal of physiology. Renal physiology · 2021Article
- Renoprotective effects of vitamin D3 supplementation in a rat model of metabolic syndrome.European journal of nutrition · 2021Article
- Antiproteinuric and Hyperkalemic Mechanisms Activated by Dual Versus Single Blockade of the RAS in Renovascular Hypertensive Rats.Frontiers in physiology · 2021Article
- ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome.Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi · 2020Review
- ACE2 as Drug Target of COVID-19 Virus Treatment, Simplified Updated Review.Reports of biochemistry & molecular biology · 2020Article
- Biological Context Linking Hypertension and Higher Risk for COVID-19 Severity.Frontiers in physiology · 2020Review
- DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications?Frontiers in pharmacology · 2020Review
- What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands.Pharmacology & therapeutics · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Proteinuria is a marker of incipient kidney injury in many disorders, including obesity. Previously, we demonstrated that megalin, a receptor endocytotic protein in the proximal tubule, is downregulated in obese mice, which was prevented by inhibition of dipeptidyl protease 4 (DPP4). Obesity is thought to be associated with upregulation of intra-renal angiotensin II (Ang II) signaling via the Ang II Type 1 receptor (AT₁R) and Ang II suppresses megalin expression in proximal tubule cells in vitro. Therefore, we tested the hypothesis that Ang II will suppress megalin protein via activation of DPP4. We used Ang II (200 ng/kg/min) infusion in mice and Ang II (10(-8) M) treatment of T35OK-AT₁R proximal tubule cells to test our hypothesis. Ang II-infused mouse kidneys displayed increases in DPP4 activity and decreases in megalin. In proximal tubule cells, Ang II stimulated DPP4 activity concurrent with suppression of megalin. MK0626, a DPP4 inhibitor, partially restored megalin expression similar to U0126, a mitogen activated protein kinase (MAPK)/extracellular regulated kinase (ERK) kinase kinase (MEK) 1/2 inhibitor and AG1478, an epidermal growth factor receptor (EGFR) inhibitor. Similarly, Ang II-induced ERK phosphorylation was suppressed with MK0626 and Ang II-induced DPP4 activity was suppressed by U0126. Therefore, our study reveals a cross talk between AT₁R signaling and DPP4 activation in the regulation of megalin and underscores the significance of targeting DPP4 in the prevention of obesity related kidney injury progression.
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Registered trials
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