ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Extracellular Vesicles from Albumin-Induced Tubular Epithelial Cells Promote the M1 Macrophage Phenotype by Targeting Klotho.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 95 citations in OpenAlex.
- The dual role of exosomes in renal fibrosis and their potential for clinical translational applications.Renal failure · 2026Review
- Loss of NGAL protects against albumin-induced kidney inflammation and fibrosis.Renal failure · 2026Article
- Extracellular Vesicle-Derived MicroRNAs as Early Diagnostic Biomarkers of Diabetic Nephropathy and Cardiovascular Diseases in Type 2 Diabetes.International journal of molecular sciences · 2026Review
- Increased WNT10B/FOXO6 signaling promotes cell fate transition in renal tubular cells to aggravate renal inflammation and fibrosis.Nature communications · 2026Article
- Leveraging extracellular vesicle biology for novel tests and therapeutics for kidney fibrosis.Clinical and translational medicine · 2026Review
- Evaluation on the significance of miR-199a-5p for preterm premature rupture of membranes with chorioamnionitis.BMC pregnancy and childbirth · 2026Article
- Shedding light on the role of extracellular vesicles in renal fibrosis.Fundamental research · 2026Review
- Cell-cell crosstalk in kidney health and disease.Nature reviews. Nephrology · 2026Review
- Nanoscale Delivery of MicroRNAs via Extracellular Vesicles: Mechanisms Potential in Modulating Cellular Senescence.International journal of nanomedicine · 2026Review
- miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease.Renal failure · 2025Article
- Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases.Military Medical Research · 2025Review
- Metformin alleviates renal tubular injury in diabetic kidney disease by activating mitophagy and inhibiting ferroptosis via HIF-1α/MIOX axis.Journal of pharmaceutical analysis · 2025Article
- DeSUMOylation of RBMX regulates exosomal sorting of cargo to promote renal tubulointerstitial fibrosis in diabetic kidney disease.Journal of advanced research · 2025Article
- Natural and engineered extracellular vesicles in vascular diseases: a focus on therapeutic effects, challenges and prospective.European journal of medical research · 2025Review
- Melatonin attenuates kidney injury by alleviating lysosomal damage in diabetic kidney disease.Acta biochimica et biophysica Sinica · 2025Article
- Exosomes and MicroRNAs: key modulators of macrophage polarization in sepsis pathophysiology.European journal of medical research · 2025Review
- Extracellular Vesicles in Renal Inflammatory Diseases: Revealing Mechanisms of Extracellular Vesicle-Mediated Macrophage Regulation.International journal of molecular sciences · 2025Review
- Extracellular Vesicle-Associated miR-ERIA Exerts the Antiangiogenic Effect of Macrophages in Diabetic Wound Healing.Diabetes · 2025Article
- Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases.Molecular biomedicine · 2025Review
- Exosomal let-7b-5p derived from Aspergillus fumigatus-treated human corneal epithelial cells promotes M1 macrophage activation via targeting SOCS-1.Frontiers in immunology · 2025Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Albumin absorbed by renal tubular epithelial cells induces inflammation and plays a key role in promoting diabetic kidney disease (DKD) progression. Macrophages are prominent inflammatory cells in the kidney, and their role there is dependent on their phenotypes. However, whether albuminuria influences macrophage phenotypes and underlying mechanisms during the development of DKD is still unclear. We found that M1 macrophage-related markers were increased in diabetes mellitus (DM) mouse renal tissues with the development of DKD, and coculture of extracellular vesicles (EVs) from human serum albumin (HSA)-induced HK-2 cells with macrophages induced macrophage M1 polarization in the presence of lipopolysaccharide (LPS). Through a bioinformatic analysis, miR-199a-5p was selected and found to be increased in EVs from HSA-induced HK-2 cells and in urinary EVs from DM patients with macroalbuminuria. Tail-vein injection of DM mice with EVs from HSA-induced HK-2 cells induced kidney macrophage M1 polarization and accelerated the progression of DKD through miR-199a-5p. miR-199a-5p exerted its effect by targeting Klotho, and Klotho induced macrophage M2 polarization through the Toll-like receptor 4 (TLR4) pathway both in vivo and in vitro. In summary, miR-199a-5p from HSA-stimulated HK-2 cell-derived EVs induces M1 polarization by targeting the Klotho/TLR4 pathway and further accelerates the progression of DKD.
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