ArticlePharmaceutical research2011
Increased liver uptake and reduced hepatic stellate cell activation with a cell-specific conjugate of the Rho-kinase inhibitor Y27632.
Article in Pharmaceutical research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Nanomedicines in the Treatment of Liver Fibrosis: A Review.International journal of nanomedicine · 2025Review
- Hepatic Stellate Cell Targeting Using Peptide-Modified Biologicals.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- Insulin-like Growth Factor-2 (IGF-2) in Fibrosis.Biomolecules · 2022Review
- Drug Targeting and Nanomedicine: Lessons Learned from Liver Targeting and Opportunities for Drug Innovation.Pharmaceutics · 2022Review
- Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases.Diabetes & metabolism journal · 2021Review
- Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy.JHEP reports : innovation in hepatology · 2021Review
- Harnessing the tunable cavity of nanoceria for enhancing Y-27632-mediated alleviation of ocular hypertension.Theranostics · 2021Article
- Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma.Nature communications · 2020Article
- Targeted Drug Delivery to Hepatic Stellate Cells for the Treatment of Liver Fibrosis.The Journal of pharmacology and experimental therapeutics · 2019Review
- AMPK agonist AICAR ameliorates portal hypertension and liver cirrhosis via NO pathway in the BDL rat model.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Rho-kinase inhibitor coupled to peptide-modified albumin carrier reduces portal pressure and increases renal perfusion in cirrhotic rats.Scientific reports · 2019Article
- Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis.World journal of gastroenterology · 2016Article
- Clinical Advancements in the Targeted Therapies against Liver Fibrosis.Mediators of inflammation · 2016Review
- An in vivo role for Rho kinase activation in the tumour vascular disrupting activity of combretastatin A-4 3-O-phosphate.British journal of pharmacology · 2014Article
- Sodium ferulate lowers portal pressure in rats with secondary biliary cirrhosis through the RhoA/Rho-kinase signaling pathway: a preliminary study.International journal of molecular medicine · 2014Article
- Future therapy of portal hypertension in liver cirrhosis - a guess.F1000prime reports · 2014Review
- CXCL12 induces hepatic stellate cell contraction through a calcium-independent pathway.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
- Enhanced effectivity of an ALK5-inhibitor after cell-specific delivery to hepatic stellate cells in mice with liver injury.PloS one · 2013Article
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
purposeRho-kinase regulates activation of hepatic stellate cells (HSC) during liver fibrosis, but the ubiquitous presence of this kinase may hinder examination of its exact role and the therapeutic use of inhibitors. We therefore coupled the Rho-kinase inhibitor Y27632 to a drug carrier that binds the mannose-6-phosphate insulin-like growth factor II (M6P/IGFII)-receptor which is upregulated on activated HSC.
methodsY27632 was coupled to mannose-6-phosphate human serum albumin (M6PHSA), and in vitro experiments were performed on primary rat HSC. Biodistribution and effect studies were performed in an acute CCl(4) model in mice.
resultsY27-conjugate remained stable in serum, while drug was efficiently released in liver homogenates. Receptor-blocking studies revealed that it was specifically taken up through the M6P/IGFII-receptor on fibroblasts, and it inhibited expression of fibrotic markers in activated HSC. In vivo, liver drug levels were significantly higher after injection of Y27-conjugate as compared to Y27632, and the conjugate accumulated specifically in HSC. After acute CCl(4)-induced liver injury, Y27-conjugate reduced the local activation of HSC, whereas an equimolar dose of free drug did not.
conclusionsWe conclude that specific targeting of a Rho-kinase inhibitor to HSC leads to enhanced accumulation of the drug in HSC, reducing early fibrogenesis in the liver.
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