ArticleWorld journal of gastroenterology2016
Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis.
Article in World journal of gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 19 citations in OpenAlex.
- Estrogen receptor β activation attenuates portal hypertension and restores mesenteric vascular reactivity in cirrhotic ratsClinical and experimental hepatology · 2026Article
- The importance of sex dimorphism in liver metabolism and progressive liver diseases.Biology of sex differences · 2025Review
- Exosome-derived tRNA fragments tRF-GluCTC-0005 promotes pancreatic cancer liver metastasis by activating hepatic stellate cells.Cell death & disease · 2024Article
- Biased Quantification of Rat Liver Fibrosis-Meta-Analysis with Practical Recommendations and Clinical Implications.Journal of clinical medicine · 2023Article
- Overexpression of estrogen receptor β inhibits cellular functions of human hepatic stellate cells and promotes the anti-fibrosis effect of calycosin via inhibiting STAT3 phosphorylation.BMC pharmacology & toxicology · 2022Article
- Sphingosine kinase 1 mediates sexual dimorphism in fibrosis in a mouse model of NASH.Molecular metabolism · 2022Article
- The Hepatoprotective and Hepatotoxic Roles of Sex and Sex-Related Hormones.Frontiers in immunology · 2022Review
- Role of noncoding RNA in the pathophysiology and treatment of intrauterine adhesion.Frontiers in genetics · 2022Review
- Saikosaponin d Alleviates Liver Fibrosis by Negatively Regulating the ROS/NLRP3 Inflammasome Through Activating the ERβ Pathway.Frontiers in pharmacology · 2022Article
- Endostatin attenuates PDGF-BB- or TGF-β1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathways.Drug design, development and therapy · 2019Article
- Research progress on signaling pathways in cirrhotic portal hypertension.World journal of clinical cases · 2018Review
- Advances in therapeutic options for portal hypertension.Therapeutic advances in gastroenterology · 2018Review
- MicroRNA-1291 promotes endometrial fibrosis by regulating the ArhGAP29-RhoA/ROCK1 signaling pathway in a murine model.Molecular medicine reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the role of diarylpropionitrile (DPN), a selective agonist of estrogen receptor β (ERβ), in liver cirrhosis with portal hypertension (PHT) and isolated hepatic stellate cells (HSCs).
methodsFemale Sprague-Dawley rats were ovariectomized (OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin (HE) and Masson's trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Collagen gel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition.
resultsTreatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance (IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of RhoA and ROCK II, and even suppressed ROCK II activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, and promoted the activities of protein kinase G (PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK II activity in activated HSCs. Finally, in vivo/in vitro experiments demonstrated that MLC activity was inhibited by DPN.
conclusionFor OVX rats with liver cirrhosis, DPN suppressed liver RhoA/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to reduced portal pressure. Therefore, DPN represents a relevant treatment choice against PHT in cirrhotic patients, especially postmenopausal women.
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