Thrombin stimulates production of fibronectin by human proximal tubular epithelial cells via a transforming growth factor-beta-dependent mechanism.

@article{Shirato2003ThrombinSP,
  title={Thrombin stimulates production of fibronectin by human proximal tubular epithelial cells via a transforming growth factor-beta-dependent mechanism.},
  author={Ken Shirato and Hiroshi Osawa and Mitsuaki Kaizuka and Norio Nakamura and Toshiyuki Sugawara and Masayuki Nakamura and Michiko Tamura and Hideaki Yamabe and Ken Okumura},
  journal={Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association},
  year={2003},
  volume={18 11},
  pages={
          2248-54
        }
}
  • K. Shirato, H. Osawa, +6 authors K. Okumura
  • Published 1 November 2003
  • Medicine
  • Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
BACKGROUND Tubulointerstitial fibrosis contributes to the progression of many forms of glomerular disease and to end-stage renal failure. Inflammatory mediators generated during glomerular injury may induce tubulointerstitial lesions by stimulating tubular cells. Thrombin has multiple biological functions in addition to its role in haemostasis and has been detected in the urine of patients with glomerular diseases. The present study investigated whether thrombin can modulate the production of… 
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Thrombin is a potential unrecognised fibroblast agonist in renal disease and further studies of thrombin and its receptors may yield valuable insights into the pathogenesis of interstitial fibrosis.
Thrombin down‐regulates the TGF‐β‐mediated synthesis of collagen and fibronectin by human proximal tubule epithelial cells through the EPCR‐dependent activation of PAR‐1
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It is shown that HK‐2 cells express endothelial protein C receptor (EPCR) and that the occupancy of this receptor by protein C switches the signaling specificity of thrombin so that the activation of PAR‐1 by throm bin inhibits the TNF‐α‐mediated synthesis of IL‐6 and IL‐8 and down‐regulates the TGF‐β‐mediated expression of ECM proteins.
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Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target.
  • A. Parrish
  • Biology, Medicine
    Progress in molecular biology and translational science
  • 2017
TLDR
Studies suggesting that MMPs and TIMPs may be biomarkers of renal dysfunction and represent novel therapeutic targets to attenuate kidney disease are summarized.
Quantitative proteomic profiling of extracellular matrix and site-specific collagen post-translational modifications in an in vitro model of lung fibrosis
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Results show, for the first time, that TGF-β1 can modulate prolyl-3-hydroxylation and glycosylation in a site-specific manner and lays the foundation for dissecting their key roles in health and disease.
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References

SHOWING 1-10 OF 22 REFERENCES
Thrombin stimulates production of transforming growth factor-beta by cultured human mesangial cells.
  • H. Yamabe, H. Osawa, +6 authors K. Onodera
  • Medicine, Biology
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 1997
TLDR
It is suggested that thrombin may modulate the synthesis of TGF-beta via protein kinase C- and tyrosine kinase-dependent mechanisms in cultured HMC and participate in the accumulation of extracellular matrix in glomeruli through the augmentation of T GF-beta production.
Thrombin stimulates synthesis of type IV collagen and tissue inhibitor of metalloproteinases-1 by cultured human mesangial cells.
TLDR
It is suggested that thrombin may contribute to the excessive accumulation of ECM and progression of glomerulosclerosis through an increase of type IV collagen production and a decreased matrix degradation presumably via a transforming growth factor-beta-dependent mechanism.
Cultured rat glomerular epithelial cells show gene expression and production of transforming growth factor-beta: expression is enhanced by thrombin.
TLDR
Thrombin may participate in the progression ofglomerulosclerosis in crescentic glomerulonephritis through the stimulation of TGF-beta production by GEC through the stimulated production of type IV collagen and fibronectin by G EC.
Regenerative and proinflammatory effects of thrombin on human proximal tubular cells.
TLDR
Thrombin might represent a powerful regenerative and proinflammatory stimulus for human proximal tubular cells (hPTC) in acute and chronic tubulointerstitial diseases.
Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy.
TLDR
Proteinuria-induced progressive renal interstitial fibrosis may be caused by glomerular ultrafiltration of high molecular weight bioactive growth factors, HGF and TGF-beta, which "activate" tubular cells through apical membranes.
Transforming growth factor-beta protein and mRNA in glomeruli in normal and diseased human kidneys.
TLDR
It is indicated that mature TGF-beta and T GF-beta-LAP are localized in association with the matrix components of GBM or mesangium, and with immune deposits in human glomeruli, and may contribute to the mesangial matrix increase.
Protease-Activated Receptor 1 Mediates Thrombin-Dependent, Cell-Mediated Renal Inflammation in Crescentic Glomerulonephritis
TLDR
Results indicate that activation of PAR-1 by thrombin or TRAP amplifies crescentic GN, which means that in addition to its procoagulant role, throm bin has proinflammatory,PAR-1–dependent effects that augment inflammatory renal injury.
Interleukin 6 production by human proximal tubular epithelial cells in vitro: analysis of the effects of interleukin-1α (IL-1α) and other cytokines
TLDR
Proximal tubular epithelial cells from human renal tissue obtained from biopsy or nephrectomy and evaluated in vitro for interleukin 6 production showed an increased IL-6 production on exposure to IL-1 alpha varying from 1.3- to 24-fold increase over baseline production, indicating de-novo synthesis.
Protein Overload Activates Proximal Tubular Cells to Release Vasoactive and Inflammatory Mediators
TLDR
Experimental evidence is available showing that protein overload per se activates proximal tubular epithelial cells in culture to upregulate genes encoding for endothelin, chemokines and cytokines, which would favor recruitment and activation of inflammatory cells into the renal interstitium and fibrogenic reaction leading to renal scarring.
Distribution of fibronectin isoforms in human renal disease
TLDR
Results show that in various renal diseases, oncofetal FN and ED‐A‐ and Ed‐B‐positive isoforms of FN accumulate at locations of chronic lesions, independently of the aetiology of the disease.
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1
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