ArticleDisease models & mechanisms2015
Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy.
Article in Disease models & mechanisms, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 74 citations in OpenAlex.
- Tubulointerstitial inflammation in glomerular diseases: mechanistic pathways, prognostic value, and translational therapeutic targets.Renal failure · 2026Review
- The role of classical protein tyrosine phosphatases in diabetic kidney disease and therapeutic implications.Journal of biomedical science · 2026Review
- Progression of diabetic nephropathy and adverse renal outcomes: possible involvement of Toll-like receptor 4 expression.Clinical and experimental nephrology · 2026Article
- CD4Frontiers in immunology · 2026Review
- Tubulointerstitial inflammation and fibrosis induced by proteinuria: fresh insights.Frontiers in pharmacology · 2026Review
- Kidney Tubular Biomarkers in Type 1 Diabetes - Longitudinal Analysis of 2 Cohorts.Kidney international reports · 2025Article
- Comprehensive Analysis and Experimental Validation of Immune-Related Biomarkers and Immune Microenvironment in Diabetic Nephropathy.Journal of inflammation research · 2025Article
- Renal protective roles of macrophage matrix metalloproteinase-12 in mice with obstructed kidneys.International journal of experimental pathology · 2024Article
- Disulfiram downregulates ferredoxin 1 to maintain copper homeostasis and inhibit inflammation in cerebral ischemia/reperfusion injury.Scientific reports · 2024Article
- Capsaicin combined with stem cells improved mitochondrial dysfunction in PIG3V cells, an immortalized human vitiligo melanocyte cell line, by inhibiting the HSP70/TLR4/mTOR/FAK signaling axis.Molecular biology reports · 2024Article
- The role of innate immunity in diabetic nephropathy and their therapeutic consequences.Journal of pharmaceutical analysis · 2024Review
- Alpha-kinase1 promotes tubular injury and interstitial inflammation in diabetic nephropathy by canonical pyroptosis pathway.Biological research · 2023Article
- The capacity of exosomes derived from adipose-derived stem cells to enhance wound healing in diabetes.Frontiers in pharmacology · 2023Review
- Immunometabolic rewiring of tubular epithelial cells in kidney disease.Nature reviews. Nephrology · 2022Review
- Albumin-induced premature senescence in human renal proximal tubular cells and its relationship with intercellular fibrosis.Acta biochimica et biophysica Sinica · 2022Article
- Signaling pathways of chronic kidney diseases, implications for therapeutics.Signal transduction and targeted therapy · 2022Review
- Chrysin ameliorates STZ-induced diabetes in rats: possible impact of modulation of TLR4/NF-κβ pathway.Research in pharmaceutical sciences · 2022Article
- Association of metabolic syndrome traits with urinary biomarkers in Japanese adults.Diabetology & metabolic syndrome · 2022Article
- Heat Shock Proteins 70 Regulate Cell Motility and Invadopodia-Associated Proteins Expression in Oral Squamous Cell Carcinoma.Frontiers in endocrinology · 2022Article
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12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased urinary albumin excretion is not simply an aftermath of glomerular injury, but is also involved in the progression of diabetic nephropathy (DN). Whereas Toll-like receptors (TLRs) are incriminated in the renal inflammation of DN, whether and how albumin is involved in the TLR-related renal inflammatory response remains to be clarified. Here, we showed that both TLR2 and TLR4, one of their putative endogenous ligands [heat shock protein 70 (HSP70)] and nuclear factor-κB promoter activity were markedly elevated in the kidneys of diabetic mice. A deficiency of TLR4 but not of TLR2 alleviated albuminuria, tubulointerstitial fibrosis and inflammation induced by diabetes. The protection against renal injury in diabetic Tlr4(-/-) mice was associated with reduced tubular injuries and preserved cubilin levels, rather than amelioration of glomerular lesions. In vitro studies revealed that albumin, a stronger inducer than high glucose (HG), induced the release of HSP70 from proximal tubular cells. HSP70 blockade ameliorated albumin-induced inflammatory mediators. HSP70 triggered the production of inflammatory mediators in a TLR4-dependent manner. Moreover, HSP70 inhibition in vivo ameliorated diabetes-induced albuminuria, inflammatory response and tubular injury. Finally, we found that individuals with DN had higher levels of TLR4 and HSP70 in the dilated tubules than non-diabetic controls. Thus, activation of the HSP70-TLR4 axis, stimulated at least in part by albumin, in the tubular cell is a newly identified mechanism associated with induction of tubulointerstitial inflammation and aggravation of pre-existing microalbuminuria in the progression of DN.
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