Relaxin modulates human and rat hepatic myofibroblast function and ameliorates portal hypertension in vivo

@article{Fallowfield2014RelaxinMH,
  title={Relaxin modulates human and rat hepatic myofibroblast function and ameliorates portal hypertension in vivo},
  author={J. Fallowfield and A. Hayden and V. Snowdon and Rebecca L. Aucott and B. Stutchfield and D. Mole and A. Pellicoro and T. Gordon-Walker and Alexander Henke and J. Schrader and P. Trivedi and M. Princivalle and S. Forbes and J. Collins and J. Iredale},
  journal={Hepatology},
  year={2014},
  volume={59}
}
Active myofibroblast (MF) contraction contributes significantly to the increased intrahepatic vascular resistance that is the primary cause of portal hypertension (PHT) in cirrhosis. We sought proof of concept for direct therapeutic targeting of the dynamic component of PHT and markers of MF activation using short‐term administration of the peptide hormone relaxin (RLN). We defined the portal hypotensive effect in rat models of sinusoidal PHT and the expression, activity, and function of the… Expand
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Treatment with relaxin reduces scarring due to excess collagen deposition by inhibiting collagen production while simultaneously promoting its degradation and can reduce established fibrosis in several animal models of extracellular matrix-associated disease, including liver fibrosis. Expand
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It is shown that hepatic macrophages play a key role in mediating the antifibrotic effects of relaxin in animal models and a nanotechnology-based approach to alleviate liver fibrosis is proposed. Expand
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TLDR
The absence/altered expression of relaxin receptor RXFP1 in the affected fibroblasts of SSc patients could explain the inefficacy of Relaxin-based anti-fibrotic treatments in the disease. Expand
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TLDR
Testing the therapeutic effects of recently identified small molecule agonists of the human relaxin receptor, relaxin family peptide receptor 1 (RXFP1) demonstrated antifibrotic effects in liver fibrosis, as evidenced by the sustained concentrations of compound in the liver. Expand
Engineered Relaxin as theranostic nanomedicine to diagnose and ameliorate liver cirrhosis.
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RLX-SPIONs are presented as a novel theranostic nanomedicine that provides new opportunities for the diagnosis and treatment of liver cirrhosis and showed enhanced contrast in MR imaging. Expand
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References

SHOWING 1-10 OF 42 REFERENCES
Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo
TLDR
Exposure of activated HSC to relaxin modulates effective collagen deposition by HSC, at least in part, due to changes in the pattern of matrix degradation, which is demonstrated to be a concentration dependent decrease in both collagen synthesis and deposition. Expand
Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers.
TLDR
In advanced fibrosis and in cirrhosis, regardless of cause or species, three distinct mesenchymal (myo)fibroblast-like liver cell subpopulations can be discerned: portal/septal MF, interface MF and perisinusoidally located HSC. Expand
Impaired endothelial nitric oxide synthase activity associated with enhanced caveolin binding in experimental cirrhosis in the rat.
TLDR
Evidence is provided that enhanced expression and interaction of caveolin with eNOS contribute to impaired NO production, reduced NOS activity, and vasoconstriction in the intact cirrhotic liver. Expand
Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: endothelial dysfunction in portal hypertension.
TLDR
SECs are an important source of EcNOS in the liver; although ecNOS mRNA and protein levels in SECs do not seem to vary with liver injury, ecNos function is altered, resulting in diminished NO release in SECS from cirrhotic livers. Expand
The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the Smad2 pathway.
BACKGROUND The peptide hormone relaxin has been demonstrated to exert antifibrotic effects in renal and extrarenal tissues. The aims of this study were to identify potential anti-fibrotic effects ofExpand
Broad-Spectrum Matrix Metalloproteinase Inhibition Curbs Inflammation and Liver Injury but Aggravates Experimental Liver Fibrosis in Mice
TLDR
Inhibition of MMP and TACE activity with Marimastat during chronic CCl4 administration counterbalanced any beneficial anti-inflammatory effect, resulting in a positive balance of collagen deposition. Expand
Liver function improvement following increased portal blood flow in cirrhotic rats.
TLDR
Investigating the effects of increased portal blood flow on hepatic microcirculation and drug elimination in 13 perfused livers from cirrhotic rats found it induces a decrease in intrahepatic resistance without changes in intra hepatic shunting and improves drug elimination by the liver without deleterious effects on hepatocyte viability. Expand
Impact of gender and endothelin on renal vasodilation and hyperfiltration induced by relaxin in conscious rats.
TLDR
It is concluded that relaxin induces marked changes in the renal circulation and in osmoregulation regardless of gender and relaxin-induced renal vasodilation and hyperfiltration are mediated by endothelin through the endothelial ET(B) receptor subtype and NO. Expand
Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors.
TLDR
It is suggested that apoptosis of activated HSC may vitally contribute to resolution of fibrosis by acting as a mechanism for removing the cell population responsible for both producing fibrotic neomatrix and protecting this matrix from degradation via their production of TIMPs. Expand
Hepatic stellate cells express the low affinity nerve growth factor receptor p75 and undergo apoptosis in response to nerve growth factor stimulation.
We have examined the expression of p75, a member of the TNF receptor superfamily in hepatic stellate cells (HSC) and pancreatic stellate cells (PSC). Activated HSC and PSC were demonstrated byExpand
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