ArticleScientific reports2020
Asymmetric dimethylarginine (ADMA) accelerates renal cell fibrosis under high glucose condition through NOX4/ROS/ERK signaling pathway.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Endocrine disorders linked to chronic kidney disease: Mechanisms and clinical implications.World journal of nephrology · 2026Review
- Nitric Oxide Signaling in Cardiovascular Physiology and Pathology: Mechanisms, Dysregulation, and Therapeutic Frontiers.International journal of molecular sciences · 2026Review
- Gut-Derived Metabolomic Biomarkers as Mediators of the Inflammatory Pathway in Early Diabetic Kidney Disease.International journal of molecular sciences · 2025Article
- Trans-Omic Analysis Identifies the 'PRMT1-STAT3-Integrin αVβ6 Axis' as a Novel Therapeutic Target in Tacrolimus-Induced Chronic Nephrotoxicity.International journal of molecular sciences · 2025Article
- The Non-Traditional Cardiovascular Culprits in Chronic Kidney Disease: Mineral Imbalance and Uremic Toxin Accumulation.International journal of molecular sciences · 2025Review
- Early Cardiovascular and Metabolic Benefits of rhGH Therapy in Adult Patients with Severe Growth Hormone Deficiency: Impact on Oxidative Stress Parameters.International journal of molecular sciences · 2025Article
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- Pleiotropic attenuating effect ofChinese herbal medicines · 2024Article
- Lesser-Explored Edible Flowers as a Choice of Phytochemical Sources for Food Applications.International journal of food science · 2024Review
- Quantitative, Targeted Analysis of Gut Microbiota Derived Metabolites Provides Novel Biomarkers of Early Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.Biomolecules · 2023Article
- Role of ADMA in the pathogenesis of microvascular complications in type 2 diabetes mellitus.Frontiers in endocrinology · 2023Review
- Serum Metabolites and Kidney Outcomes: The Atherosclerosis Risk in Communities Study.Kidney medicine · 2022Article
- DDAH1/ADMA Regulates Adiponectin Resistance in Cerebral Ischemia via the ROS/FOXO1/APR1 Pathway.Oxidative medicine and cellular longevity · 2022Article
- Progress of Statin Therapy in the Treatment of Idiopathic Pulmonary Fibrosis.Oxidative medicine and cellular longevity · 2022Review
- Pathophysiology of Hypertension: The Mosaic Theory and Beyond.Circulation research · 2021Review
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Authors and funding
7 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
We previously reported that the circulatory level of Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, was increased in diabetic kidney disease patients. However, the mechanism and the role of ADMA in diabetic kidney injury remain unclear. Hence, our principal aim is to investigate the causal role of ADMA in the progression of renal cell fibrosis under high glucose (HG) treatment and to delineate its signaling alterations in kidney cell injury. High Glucose/ADMA significantly increased fibrotic events including cell migration, invasion and proliferation along with fibrotic markers in the renal cells; whereas ADMA inhibition reversed the renal cell fibrosis. To delineate the central role of ADMA induced fibrotic signaling pathway and its downstream signaling, we analysed the expression levels of fibrotic markers, NOX4, ROS and ERK activity by using specific inhibitors and genetic manipulation techniques. ADMA stimulated the ROS generation along with a significant increase in NOX4 and ERK activity. Further, we observed that ADMA activated NOX-4 and ERK are involved in the extracellular matrix proteins accumulation. Also, we observed that ADMA induced ERK1/2 phosphorylation was decreased after NOX4 silencing. Our study mechanistically demonstrates that ADMA is involved in the progression of kidney cell injury under high glucose condition by targeting coordinated complex mechanisms involving the NOX4- ROS-ERK pathway.
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