ArticleBritish journal of pharmacology2019
Blockade of myeloid differentiation 2 attenuates diabetic nephropathy by reducing activation of the renin-angiotensin system in mouse kidneys.
Article in British journal of pharmacology, 2019. 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 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Diabetic kidney disease: from pathogenesis to multimodal therapy-current evidence and future directions.Frontiers in medicine · 2025Review
- The role of innate immunity in diabetic nephropathy and their therapeutic consequences.Journal of pharmaceutical analysis · 2024Review
- Azelaic Acid Regulates the Renin-Angiotensin System and Improves Colitis Based on Network Pharmacology and Experimentation.ACS omega · 2023Article
- The Molecular Mechanism of Renal Tubulointerstitial Inflammation Promoting Diabetic Nephropathy.International journal of nephrology and renovascular disease · 2023Review
- Signaling pathways of chronic kidney diseases, implications for therapeutics.Signal transduction and targeted therapy · 2022Review
- Pharmacological inhibition of MyD88 suppresses inflammation in tubular epithelial cells and prevents diabetic nephropathy in experimental mice.Acta pharmacologica Sinica · 2022Article
- Formyl peptide receptor 1 promotes podocyte injury through regulation of mitogen-activated protein kinase pathways.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- circ_000166/miR-296 Aggravates the Process of Diabetic Renal Fibrosis by Regulating the SGLT2 Signaling Pathway in Renal Tubular Epithelial Cells.Disease markers · 2022Article
- MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway.Journal of gastrointestinal oncology · 2021Article
- Crosstalk of TLR4, vascular NADPH oxidase, and COVID-19 in diabetes: What are the potential implications?Vascular pharmacology · 2021Review
- Galangin attenuates oxidative stress-mediated apoptosis in high glucose-induced renal tubular epithelial cells through modulating renin-angiotensin system and PI3K/AKT/mTOR pathway.Toxicology research · 2021Article
- Article
- Stimulation of Angiotensin Converting Enzyme 2: A Novel Treatment Strategy for Diabetic Nephropathy.Frontiers in physiology · 2021Review
- Carnosine alleviates diabetic nephropathy by targeting GNMT, a key enzyme mediating renal inflammation and fibrosis.Clinical science (London, England : 1979) · 2020Article
- Blockade of the TLR4-MD2 complex lowers blood pressure and improves vascular function in a murine model of type 1 diabetes.Scientific reports · 2020Article
- Selective targeting of the TLR4 co-receptor, MD2, prevents colon cancer growth and lung metastasis.International journal of biological sciences · 2020Article
- The Interplay of Renin-Angiotensin System and Toll-Like Receptor 4 in the Inflammation of Diabetic Nephropathy.Journal of immunology research · 2020Review
- Inhibition of STAT3 in tubular epithelial cells prevents kidney fibrosis and nephropathy in STZ-induced diabetic mice.Cell death & disease · 2019Article
- Blockade of myeloid differentiation 2 attenuates diabetic nephropathy by reducing activation of the renin-angiotensin system in mouse kidneys.British journal of pharmacology · 2019Article
Corrections and comments
- Erratum issuedCorrection.2021
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeBoth innate immunity and the renin-angiotensin system (RAS) play important roles in the pathogenesis of diabetic nephropathy (DN). Myeloid differentiation factor 2 (MD2) is a co-receptor of toll-like receptor 4 (TLR4) in innate immunity. While TLR4 is involved in the development of DN, the role of MD2 in DN has not been characterized. It also remains unclear whether the MD2/TLR4 signalling pathway is associated with RAS activation in diabetes. EXPERIMENTAL APPROACH: MD2 was blocked using siRNA or the low MW inhibitor, L6H9, in renal proximal tubular cells (NRK-52E cells) exposed to high concentrations of glucose (HG). In vivo, C57BL/6 and MD2 KEY
resultsInhibition of MD2 by genetic knockdown or the inhibitor L6H9 suppressed HG-induced expression of ACE and angiotensin receptors and production of angiotensin II in NRK-52E cells, along with decreased fibrosis markers (TGF-β and collagen IV). Inhibition of the MD2/TLR4-MAPKs pathway did not affect HG-induced renin overproduction. In vivo, using the streptozotocin-induced diabetic mice, MD2 was overexpressed in diabetic kidney. MD2 gene knockout or L6H9 attenuated renal fibrosis and dysfunction by suppressing local RAS activation and inflammation. CONCLUSIONS AND IMPLICATIONS: Hyperglycaemia activated the MD2/TLR4-MAPKs signalling cascade to induce renal RAS activation, leading to renal fibrosis and dysfunction. Pharmacological inhibition of MD2 may be considered as a therapeutic approach to mitigate DN and the low MW inhibitor L6H9 could be a candidate for such therapy.
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