ArticlePloS one2013
Enhanced effectivity of an ALK5-inhibitor after cell-specific delivery to hepatic stellate cells in mice with liver injury.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Exploring the Therapeutic Potential of TGF-β Inhibitors for Liver Fibrosis: Targeting Multiple Signaling Pathways.Journal of clinical and translational hepatology · 2025Review
- Mechanism and Progress of Natural Products in the Treatment of NAFLD-Related Fibrosis.Molecules (Basel, Switzerland) · 2023Review
- Liver Cell Type-Specific Targeting by Nanoformulations for Therapeutic Applications.International journal of molecular sciences · 2023Review
- The progress of autoimmune hepatitis research and future challenges.Open medicine (Warsaw, Poland) · 2023Review
- Hepatic Stellate Cell Targeting Using Peptide-Modified Biologicals.Methods in molecular biology (Clifton, N.J.) · 2023Article
- 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
- TGF-β signaling in liver metastasis.Clinical and translational medicine · 2020Review
- Targeting Cancer Associated Fibroblasts in Liver Fibrosis and Liver Cancer Using Nanocarriers.Cells · 2020Review
- [Research progress of receptor targeted hepatic stellate cell in treatment of liver fibrosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2018Review
- P311, Friend, or Foe of Tissue Fibrosis?Frontiers in pharmacology · 2018Review
- Nanotechnology in Glycomics: Applications in Diagnostics, Therapy, Imaging, and Separation Processes.Medicinal research reviews · 2017Review
- Glucocorticoids Have Opposing Effects on Liver Fibrosis in Hepatic Stellate and Immune Cells.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors.JCI insight · 2016Article
- Clinical Advancements in the Targeted Therapies against Liver Fibrosis.Mediators of inflammation · 2016Review
- Potential Use of Biological Proteins for Liver Failure Therapy.Pharmaceutics · 2015Review
- Diverse origins of the myofibroblast—implications for kidney fibrosis.Nature reviews. Nephrology · 2015Review
- Angiotensin II stimulates canonical TGF-β signaling pathway through angiotensin type 1 receptor to induce granulation tissue contraction.Journal of molecular medicine (Berlin, Germany) · 2015Article
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
Transforming growth factor-β (TGF-β) is a major pro-fibrotic cytokine, causing the overproduction of extracellular matrix molecules in many fibrotic diseases. Inhibition of its type-I receptor (ALK5) has been shown to effectively inhibit fibrosis in animal models. However, apart from its pro-fibrotic effects, TGF-β also has a regulatory role in the immune system and influences tumorigenesis, which limits the use of inhibitors. We therefore explored the cell-specific delivery of an ALK5-inhibitor to hepatic stellate cells, a key cell in the development of liver fibrosis. We synthesized a conjugate of the ALK5-inhibitor LY-364947 coupled to mannose-6-phosphate human serum albumin (M6PHSA), which binds to the insulin-like growth factor II receptor on activated HSC. The effectivity of the conjugate was evaluated in primary HSC and in an acute liver injury model in mice. In vitro, the free drug and the conjugate significantly inhibited fibrotic markers in HSC. In hepatocytes, TGF-β-dependent signaling was inhibited by free drug, but not by the conjugate, thus showing its cell-specificity. In vivo, the conjugate localized in desmin-positive cells in the liver and not in hepatocytes or immune cells. In the acute liver injury model in mice, the conjugate reduced fibrogenic markers and collagen deposition more effectively than free drug. We conclude that we can specifically deliver an ALK5-inhibitor to HSC using the M6PHSA carrier and that this targeted drug reduces fibrogenic parameters in vivo, without affecting other cell-types.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.