Relaxin receptors in hepatic stellate cells and cirrhotic liver

Bennett, Robert G.; Dalton, Shana R.; Mahan, Katrina J.; Gentry-Nielsen, Martha J.; Hamel, Frederick G.; Tuma, Dean J.

doi:10.1016/j.bcp.2006.12.007

Cited by 31 publications

(29 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the liver, the myofibroblastic hepatic stellate cells are the predominant RXFP1-expressing cells (31,32). A human hepatic stellate cell line (LX2) that recapitulates many of the properties of activated hepatic stellate cells (27) was used.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Relaxin Activates Peroxisome Proliferator-activated Receptor γ (PPARγ) through a Pathway Involving PPARγ Coactivator 1α (PGC1α)

Singh

Simpson

Bennett

2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Relaxin activates peroxisome proliferator-activated receptor ␥ (PPAR␥) by an unknown PPAR␥ ligandindependent mechanism. Results: Expression of PPAR␥ coactivator 1␣ (PGC1␣) was increased by relaxin through distinct signaling pathways. Conclusion:The mechanism for relaxin regulation of PPAR␥ is through increased PGC1␣ levels. Significance: Discovery of new targets of relaxin signaling may provide further understanding of its pleiotropic effects.

show abstract

Section: Resultsmentioning

confidence: 99%

“…**, p Ͻ .01; ***, p Ͻ .001. (31,52). In this study, we used LX2 cells, a human hepatic stellate cell line that recapitulates many of the properties of primary cells (27).…”

Section: Discussionmentioning

confidence: 99%

Relaxin Activates Peroxisome Proliferator-activated Receptor γ (PPARγ) through a Pathway Involving PPARγ Coactivator 1α (PGC1α)

Singh

Simpson

Bennett

2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The primary antibody against Rxfp2 was rabbit anti-human LGR8 (737–754) (H001-54, Phoenix Pharmaceuticals). Both antibodies recognize rat proteins and have been well characterized for human [29,30] and rat tissues [31,32]. The sections were rinsed 3 times, 5 min each, with the blocking buffer, and incubated for 1 h with the secondary antibody (1:300 dilution of biotinylated goat anti-rabbit IgG (Santa Cruz Biotechnologies, Santa Cruz, CA).…”

Section: Methodsmentioning

confidence: 99%

Relaxin family peptide receptors Rxfp1 and Rxfp2: mapping of the mRNA and protein distribution in the reproductive tract of the male rat

Filonzi

Cardoso

Pimenta

et al. 2007

Reprod Biol Endocrinol

View full text Add to dashboard Cite

Background: Relaxin is the endogenous ligand of the G-protein coupled receptor RXFP1, previously known as LGR7. In humans relaxin can also activate, but with lower affinity, the closely related receptor for the insulin-like peptide from Leydig cells, RXFP2, previously known as LGR8. The lack of relaxin impairs male fertility but the precise distribution and the function of relaxin receptors in the male reproductive tract is not known. We investigated the distribution of Rxfp1 and Rxfp2 in the reproductive tract of the male rat and the function of relaxin in the vas deferens, a tissue with high expression of both receptors.

show abstract

“…Relaxin promoted a matrix degrading phenotype in HSCs by increasing matrix metalloproteinase expression and activity, and inhibiting secretion of the tissue inhibitors of metalloproteinases[10,11]. The effects of relaxin were mediated by activation of the relaxin family peptide 1 (RXFP1) receptor, which is expressed predominantly in the HSC in liver[12,13]. Finally, using in vivo models of experimental hepatic fibrosis, relaxin prevented hepatic collagen content[10,14], and was effective in treating established hepatic fibrosis[13,15].…”

Section: Introductionmentioning

confidence: 99%

Serelaxin increases the antifibrotic action of rosiglitazone in a model of hepatic fibrosis

Bennett

Simpson

Hamel

2017

WJG

View full text Add to dashboard Cite

AIMTo determine the effect of combined serelaxin and rosiglitazone treatment on established hepatic fibrosis.METHODSHepatic fibrosis was induced in mice by carbon tetrachloride administration for 6 wk, or vehicle alone (nonfibrotic mice). For the final 2 wk, mice were treated with rosiglitazone, serelaxin, or both rosiglitazone and serelaxin. Serum liver enzymes and relaxin levels were determined by standard methods. The degree of liver collagen content was determined by histology and immunohistochemistry. Expression of type I collagen was determined by quantitative PCR. Activation of hepatic stellate cells was assessed by alpha-smooth muscle actin (SMA) levels. Liver peroxisome proliferator activated receptor-gamma coactivator 1 alpha (PGC1α) was determined by Western blotting.RESULTSTreatment of mice with CCl4 resulted in hepatic fibrosis as evidenced by increased liver enzyme levels (ALT and AST), and increased liver collagen and SMA. Monotherapy with either serelaxin or rosiglitazone for 2 wk was generally without effect. In contrast, the combination of serelaxin and rosiglitazone resulted in significantly improved ALT levels (P < 0.05). Total liver collagen content as determined by Sirius red staining revealed that only combination treatment was effective in reducing total liver collagen (P < 0.05). These results were supported by immunohistochemistry for type I collagen, in which only combination treatment reduced fibrillar collagen levels (P < 0.05). The level of hepatic stellate cell activation was modestly, but significantly, reduced by serelaxin treatment alone, but combination treatment resulted in significantly lower SMA levels. Finally, while hepatic fibrosis reduced liver PGC1α levels, the combination of serelaxin and rosiglitazone resulted in restoration of PGC1α protein levels.CONCLUSIONThe combination of serelaxin and rosiglitazone treatment for 2 wk was effective in significantly reducing established hepatic fibrosis, providing a potential new treatment strategy.

show abstract

Relaxin receptors in hepatic stellate cells and cirrhotic liver

Cited by 31 publications

References 39 publications

Relaxin Activates Peroxisome Proliferator-activated Receptor γ (PPARγ) through a Pathway Involving PPARγ Coactivator 1α (PGC1α)

Relaxin Activates Peroxisome Proliferator-activated Receptor γ (PPARγ) through a Pathway Involving PPARγ Coactivator 1α (PGC1α)

Relaxin family peptide receptors Rxfp1 and Rxfp2: mapping of the mRNA and protein distribution in the reproductive tract of the male rat

Serelaxin increases the antifibrotic action of rosiglitazone in a model of hepatic fibrosis

Contact Info

Product

Resources

About