ArticleJournal of cellular physiology2019
Thrombin cleavage of osteopontin controls activation of hepatic stellate cells and is essential for liver fibrogenesis.
Article in Journal of cellular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Context-dependent roles of osteopontin in aging-related neurological disorders.The Journal of international medical research · 2026Review
- Identification of Schwann Cells in Human Intracranial Arteries: Potential Regulatory Role in Atherosclerotic Plaque Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- H4K12 Lactylation Activated-Spp1 in Reprogrammed Microglia Improves Functional Recovery After Spinal Cord Injury.CNS neuroscience & therapeutics · 2025Article
- SPP1 is a plasma biomarker associated with the dia gnosis and prediction of prognosis in sepsis.Scientific reports · 2024Article
- The Multifaceted Role of Osteopontin in Prostate Pathologies.Biomedicines · 2023Review
- Review
- Osteopontin as a Biomarker in Chronic Kidney Disease.Biomedicines · 2023Review
- Identification of LBH and SPP1 involved in hepatic stellate cell activation during liver fibrogenesis.Human cell · 2023Article
- Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS).International immunology · 2023Review
- Osteopontin May Improve Postinjury Muscle Repair Via Matrix Metalloproteinases And tgf-β Activation in Regular Exercise.International journal of medical sciences · 2023Article
- Osteopontin Exacerbates High-Fat Diet-Induced Metabolic Disorders in a Microbiome-Dependent Manner.mBio · 2022Article
- Clinical and Molecular Implications of Osteopontin in Heart Failure.Current issues in molecular biology · 2022Review
- Pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.World journal of clinical cases · 2022Review
- Osteopontin aggravates acute lung injury in influenza virus infection by promoting macrophages necroptosis.Cell death discovery · 2022Article
- Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases.Biomedicines · 2021Review
- Osteopontin Takes Center Stage in Chronic Liver Disease.Hepatology (Baltimore, Md.) · 2021Review
- Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice.Frontiers in cell and developmental biology · 2021Article
- Integrin-α9β1 as a Novel Therapeutic Target for Refractory Diseases: Recent Progress and Insights.Frontiers in immunology · 2021Review
- Prostatic osteopontin expression is associated with symptomatic benign prostatic hyperplasia.The Prostate · 2020Article
- Effect of NLRC5 on activation and reversion of hepatic stellate cells by regulating the nuclear factor-κB signaling pathway.World journal of gastroenterology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Liver biopsy is the current reliable way of evaluating liver fibrosis. However, no specific sera biomarker could be applied in clinical diagnosis. As the pivotal role of osteopontin (OPN) reported in numerous liver diseases, thrombin-cleaved OPN (Thr-OPN) exposes an integrin-binding motif that promoted biological functions. Herein, we investigated the potential of Thr-OPN in liver fibrosis. Using patient samples, mouse models and hepatic stellate cells (HSCs), we analyzed the involvement of Thr-OPN in liver fibrosis. The result showed that, first, Thr-OPN level was significantly higher in patients with liver cirrhosis than that in patients with chronic hepatitis B and healthy controls. Thr-OPN level was positively correlated with liver fibrosis degree in clinical samples. Then in mouse models, it showed a similar correlation between hepatic Thr-OPN levels and liver fibrosis degree. Thr-OPN peptides exacerbated liver fibrosis in OPN-deficient mice, whereas the neutralization of Thr-OPN alleviated liver fibrosis in wild-type mice. Furthermore, when compared with full-length OPN (FL-OPN), Thr-OPN exhibited a greater ability to promote HSC activation, proliferation, and migration via mitogen-activated protein (MAP) kinase and nuclear factor (NF)-κB pathways. In conclusion, Thr-OPN, not FL-OPN, was critically involved in the exacerbation of liver fibrosis by α9 and α4 integrins via MAP kinase and NF-κB signaling pathway, thus representing a novel diagnostic biomarker and treatment target for liver cirrhosis.
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