ArticleInternational journal of molecular sciences2019
LPS-Binding Protein Modulates Acute Renal Fibrosis by Inducing Pericyte-to-Myofibroblast Trans-Differentiation through TLR-4 Signaling.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- Emergence of fibrotic pericytes and their transcriptional regulation in pulmonary fibrosis.Nature communications · 2026Article
- Gallic acid attenuates LPS-induced acute kidney injury with accompanying changes in inflammatory and redox-related signaling pathways.Molecular biology reports · 2026Article
- Renal allograft interstitial fibrosis: multicellular interactions and therapeutic strategies.Frontiers in immunology · 2026Review
- Targeting the renin-angiotensin system in sepsis-associated AKI: from pathophysiology to precision medicine.Frontiers in immunology · 2026Review
- Fibroblasts in AKI: small army, big help.Trends in molecular medicine · 2025Review
- Bidirectional Role of Pericytes in Ischemic Stroke.Brain sciences · 2025Review
- Progression of Kidney Fibrosis after Sepsis: Underestimated Role of Resident Macrophages and Recruited Monocytes.Journal of the American Society of Nephrology : JASN · 2025Review
- MTHFD2 stabilizes LOX expression through RNA methylation modification to promote sepsis-induced acute kidney injury progression.Human cell · 2025Article
- Review of research progress in sepsis-associated acute kidney injury.Frontiers in molecular biosciences · 2025Review
- Dual Immunoglobulin Domain-Containing Cell Adhesion Molecule Increases Early in Renal Tubular Cell Injury and Plays Anti-Inflammatory Role.Current issues in molecular biology · 2024Article
- Exploring unconventional targets in myofibroblast transdifferentiation outside classical TGF-Frontiers in physiology · 2024Review
- Beneficial effects of recombinant CER-001 high-density lipoprotein infusion in sepsis: results from a bench to bedside translational research project.BMC medicine · 2023Article
- Toll-like Receptor 4 in Acute Kidney Injury.International journal of molecular sciences · 2023Review
- Curcumin inhibits lipopolysaccharide-induced proximal renal tubular epithelial cell death by regulating ADAMTS18 methylation and AKT/Notch pathways.Archives of medical science : AMS · 2023Article
- Stem Cell-Derived Extracellular Vesicles as Potential Therapeutic Approach for Acute Kidney Injury.Frontiers in immunology · 2022Review
- Review
- Peripheral nervous system manifestations of Shiga toxin-producing E. coli-induced haemolytic uremic syndrome in children.Italian journal of pediatrics · 2021Article
- Multifaced Roles of HDL in Sepsis and SARS-CoV-2 Infection: Renal Implications.International journal of molecular sciences · 2021Review
- The Ambivalent Role of miRNAs in Carcinogenesis: Involvement in Renal Cell Carcinoma and Their Clinical Applications.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Molecular characterization of the human kidney interstitium in health and disease.Science advances · 2021Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
During sepsis, the increased synthesis of circulating lipopolysaccharide (LPS)-binding protein (LBP) activates LPS/TLR4 signaling in renal resident cells, leading to acute kidney injury (AKI). Pericytes are the major source of myofibroblasts during chronic kidney disease (CKD), but their involvement in AKI is poorly understood. Here, we investigate the occurrence of pericyte-to-myofibroblast trans-differentiation (PMT) in sepsis-induced AKI. In a swine model of sepsis-induced AKI, PMT was detected within 9 h from LPS injection, as evaluated by the reduction of physiologic PDGFRβ expression and the dysfunctional α-SMA increase in peritubular pericytes. The therapeutic intervention by citrate-based coupled plasma filtration adsorption (CPFA) significantly reduced LBP, TGF-β, and endothelin-1 (ET-1) serum levels, and furthermore preserved PDGFRβ and decreased α-SMA expression in renal biopsies. In vitro, both LPS and septic sera led to PMT with a significant increase in Collagen I synthesis and α-SMA reorganization in contractile fibers by both SMAD2/3-dependent and -independent TGF-β signaling. Interestingly, the removal of LBP from septic plasma inhibited PMT. Finally, LPS-stimulated pericytes secreted LBP and TGF-β and underwent PMT also upon TGF-β receptor-blocking, indicating the crucial pro-fibrotic role of TLR4 signaling. Our data demonstrate that the selective removal of LBP may represent a therapeutic option to prevent PMT and the development of acute renal fibrosis in sepsis-induced AKI.
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