ArticleJournal of the American Society of Nephrology : JASN2012
Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy.
Article in Journal of the American Society of Nephrology : JASN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers, 3 of them syntheses that pooled it.
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Who cites it
203 citing papers in PubMed, 3 syntheses or guidelines pooled it, 375 citations in OpenAlex.
- Gut Microbiome in Patients with Chronic Kidney Disease Stages 4 and 5: A Systematic Literature Review.International journal of molecular sciences · 2025Pooled it
- Transcriptomic Approach in Understanding Fabry Nephropathy: A Review of the Literature and Proof-of-Concept.Genes · 2025Pooled it
- Emerging trends and focus of Toll-like receptors in kidney diseases: a 20-year bibliometric analysis.Frontiers in medicine · 2025Pooled it
- Trial
- Tubulointerstitial inflammation in glomerular diseases: mechanistic pathways, prognostic value, and translational therapeutic targets.Renal failure · 2026Review
- Inflammation as a therapeutic target to improve kidney and cardiovascular outcomes.Nature reviews. Nephrology · 2026Review
- CCL5 mRNA-enriched small extracellular vesicles from renal tubular epithelial cells enhance macrophage inflammatory responses in diabetic nephropathy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Mogroside V Alleviates Renal Injury in Diabetic Mice via Regulation of theInternational journal of molecular sciences · 2026Article
- Molecular mechanisms and novel therapeutic targets of diabetic kidney disease.Chinese medical journal · 2026Review
- Progression of diabetic nephropathy and adverse renal outcomes: possible involvement of Toll-like receptor 4 expression.Clinical and experimental nephrology · 2026Article
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- GLP-1 receptor agonists and next-generation metabolic hormone therapies in chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Inflammation and Diabetic Kidney Disease.International journal of molecular sciences · 2026Review
- Shenlian (SL) Decoction Treat Diabetic Nephropathy by Regulating M1 Polarization of Macrophages and Pyroptosis of Renal Tubular Epithelial Cells.Journal of diabetes research · 2026Article
- Gut microbiota-liver-kidney axis in diabetic kidney disease: mechanistic insights into amino acid metabolism and nutritional intervention strategies targeting natural bioactive compounds.Frontiers in nutrition · 2026Review
- Unveiling the immune microenvironment in diabetic nephropathy: from mechanisms to therapeutics.Frontiers in immunology · 2026Review
- Multidimensional mechanisms of natural products in modulating metabolic dysfunction-associated kidney disease: recent advances and future perspectives.Frontiers in pharmacology · 2026Review
- Decoding Diabetes: Hub Genes as Pivotal Players in Cardiomyopathy and Kidney Disease.Endocrine, metabolic & immune disorders drug targets · 2026Article
- PCSK9 Inhibitors: A Potential Priority Choice for Lipid Management in Patients with Diabetic Kidney Disease.Drugs · 2025Review
- Uncovering key markers and therapeutic targets for renal fibrosis in diabetic kidney disease through bulk and single-cell RNA sequencing.Journal of translational medicine · 2025Article
143 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation contributes to the tubulointerstitial lesions of diabetic nephropathy. Toll-like receptors (TLRs) modulate immune responses and inflammatory diseases, but their role in diabetic nephropathy is not well understood. In this study, we found increased expression of TLR4 but not of TLR2 in the renal tubules of human kidneys with diabetic nephropathy compared with expression of TLR4 and TLR2 in normal kidney and in kidney disease from other causes. The intensity of tubular TLR4 expression correlated directly with interstitial macrophage infiltration and hemoglobin A1c level and inversely with estimated glomerular filtration rate. The tubules also upregulated the endogenous TLR4 ligand high-mobility group box 1 in diabetic nephropathy. In vitro, high glucose induced TLR4 expression via protein kinase C activation in a time- and dose-dependent manner, resulting in upregulation of IL-6 and chemokine (C-C motif) ligand 2 (CCL-2) expression via IκB/NF-κB activation in human proximal tubular epithelial cells. Silencing of TLR4 with small interfering RNA attenuated high glucose-induced IκB/NF-κB activation, inhibited the downstream synthesis of IL-6 and CCL-2, and impaired the ability of conditioned media from high glucose-treated proximal tubule cells to induce transmigration of mononuclear cells. We observed similar effects using a TLR4-neutralizing antibody. Finally, streptozotocin-induced diabetic and uninephrectomized TLR4-deficient mice had significantly less albuminuria, renal dysfunction, renal cortical NF-κB activation, tubular CCL-2 expression, and interstitial macrophage infiltration than wild-type animals. Taken together, these data suggest that a TLR4-mediated pathway may promote tubulointerstitial inflammation in diabetic nephropathy.
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Registered trials
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.