ArticleNephron2019
Spontaneous Extracellular Matrix Accumulation in a Human in vitro Model of Renal Fibrosis Is Mediated by αV Integrins.
Article in Nephron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- A practical toolbox for modelling fibrosis in vitro.Nature biomedical engineering · 2026Review
- Jiawei Danggui Buxue Decoction Reduces Apoptosis and EMT of Renal Interstitial Fibrosis by Regulating JAK2/STAT3 Signaling Pathway.Combinatorial chemistry & high throughput screening · 2026Article
- Kidney Fibrosis In Vitro and In Vivo Models: Path Toward Physiologically Relevant Humanized Models.Advanced healthcare materials · 2025Review
- 3D Humanized Bioprinted Tubulointerstitium Model to Emulate Renal Fibrosis In Vitro.Advanced healthcare materials · 2024Article
- Article
- Identification of ligand and receptor interactions in CKD and MASH through the integration of single cell and spatial transcriptomics.PloS one · 2024Article
- Cell Adhesion Molecules in Fibrotic Diseases.Biomedicines · 2023Review
- Liquid Biopsy at the Frontier of Kidney Diseases: Application of Exosomes in Diagnostics and Therapeutics.Genes · 2023Review
- Reduced methylation correlates with diabetic nephropathy risk in type 1 diabetes.The Journal of clinical investigation · 2023Article
- NF-κB drives epithelial-mesenchymal mechanisms of lung fibrosis in a translational lung cell model.JCI insight · 2023Article
- TGF-β Inhibitors for Therapeutic Management of Kidney Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2022Review
- suPAR: An Inflammatory Mediator for Kidneys.Kidney diseases (Basel, Switzerland) · 2022Review
- Toward Human Models of Cardiorenal SyndromeFrontiers in cardiovascular medicine · 2022Review
- Article
- Collagen I Modifies Connexin-43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1-Evoked Renal Tubular Epithelial Cells.International journal of molecular sciences · 2021Article
- Cardio-protective effects of a dioxidovanadium(V) complex in male sprague-dawley rats with streptozotocin-induced diabetes.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- Renoprotective Effects of Maslinic Acid on Experimental Renal Fibrosis in Unilateral Ureteral Obstruction Model via Targeting MyD88.Frontiers in pharmacology · 2021Article
- Article
- Potential Role of Integrin α₅β₁/Focal Adhesion Kinase (FAK) and Actin Cytoskeleton in the Mechanotransduction and Response of Human Gingival Fibroblasts Cultured on a 3-Dimension Lactide-Co-Glycolide (3D PLGA) Scaffold.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- A high throughput zebrafish chemical screen reveals ALK5 and non-canonical androgen signalling as modulators of the pkd2Scientific reports · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTubulointerstitial fibrosis is a key feature of chronic kidney diseases leading to renal failure. It is characterised by the infiltration of fibroblasts and aberrant accumulation of extracellular matrix (ECM) proteins, which are associated with progressive loss of renal function. Integrins play a major role in fibrosis, but the mechanisms through which they do this are not fully understood.
objectiveUsing a complex cell system, we test the hypothesis that integrins are pro-fibrotic via regulation of functional interactions between tubular epithelial cells and renal fibroblasts.
methodContact co-culture of human primary renal proximal tubular epithelial cells and renal fibroblasts promoted the spontaneous accumulation of a mature ECM rich in interstitial collagens, which was considerably in excess of that seen in the individual mono-cultures. Both cell types persisted throughout the culture and were capable of expressing multiple ECM components.
resultsWhile ECM accumulation was inhibited by the clinically proven anti-fibrotic, nintedanib, and was partially abrogated by transforming growth factor β neutralisation, its levels did not return to basal, indicating additional pathways were implicated in the pro-ECM response. Application of anti-integrin blocking antibodies and small molecules demonstrated a major role of the αV integrins in the ECM accumulation during fibroblast: epithelial cell interactions.
conclusionIntegrin-mediated pathways can facilitate the spontaneous accumulation of ECM during fibroblast: epithelial cell interactions, and this direct renal co-culture assay system could provide a translational in vitro assay for investigating novel pathways involved in the pro-ECM response and the screening of renal anti-fibrotic agents.
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