ArticleThe Journal of biological chemistry2007
A matrix metalloproteinase-9 activation cascade by hepatic stellate cells in trans-differentiation in the three-dimensional extracellular matrix.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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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
43 citing papers in PubMed, 90 citations in OpenAlex.
- Trial
- Hepatic stellate cells in alcoholic liver cirrhosis: mechanisms of fibrogenesis, plasticity, and fibrosis reversal.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Special Issue "Alcohol and Inflammation".International journal of molecular sciences · 2026Article
- Stromal softness confines pancreatic cancer growth through lysosomal-cathepsin mediated YAP1 degradation.Cellular and molecular life sciences : CMLS · 2024Article
- Elastin stabilization prevents impaired biomechanics in human pulmonary arteries and pulmonary hypertension in rats with left heart disease.Nature communications · 2023Article
- Alcohol, Inflammation, and Microbiota in Alcoholic Liver Disease.International journal of molecular sciences · 2023Review
- SOMAscan Proteomics Identifies Novel Plasma Proteins in Amyotrophic Lateral Sclerosis Patients.International journal of molecular sciences · 2023Article
- Role of hepatic stellate cells in liver ischemia-reperfusion injury.Frontiers in immunology · 2022Review
- LncRNAInternational journal of molecular sciences · 2021Article
- Interleukin-1 Receptor Antagonist Modulates Liver Inflammation and Fibrosis in Mice in a Model-Dependent Manner.International journal of molecular sciences · 2019Article
- The Forkhead box F1 transcription factor inhibits collagen deposition and accumulation of myofibroblasts during liver fibrosis.Biology open · 2019Article
- Inflammatory pathways in alcoholic steatohepatitis.Journal of hepatology · 2019Review
- BMP-2 restoration aids in recovery from liver fibrosis by attenuating TGF-β1 signaling.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Enhancement of Silymarin Anti-fibrotic Effects by Complexation With Hydroxypropyl (HPBCD) and Randomly Methylated (RAMEB) β-Cyclodextrins in a Mouse Model of Liver Fibrosis.Frontiers in pharmacology · 2018Article
- Role of canonical Hedgehog signaling pathway in liver.International journal of biological sciences · 2018Review
- PD-1 immunobiology in autoimmune hepatitis and hepatocellular carcinoma.Seminars in oncology · 2017Review
- Matrix Metalloproteinases as Regulators of Periodontal Inflammation.International journal of molecular sciences · 2017Review
- Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis.Scientific reports · 2017Article
- Article
- Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase.Clinical and molecular hepatology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Hepatic stellate cells (HSCs) undergo myofibroblastic trans-differentiation in liver fibrogenesis. We previously showed that dual stimulation with three-dimensional type-I collagen and interleukin-1 (IL-1) synergistically induces HSC trans-differentiation in a manner dependent on the activation of matrix metallopreinase-9 (MMP-9). The present study is aimed to determine the mechanism of MMP-9 activation in this model. The pro-MMP-9-converting activities expressed by trans-differentiating HSCs are characterized as secreted factors that are sensitive to MMP inhibitor and have apparent molecular masses of 50 and 25 kDa. This is in sharp contrast to the pro-MMP-9 activator from mouse and human skin, which is a chymotrypsin-like proteinase. Among multiple MMPs induced in HSCs by the dual stimulation, MMP-13 is most conspicuously up-regulated and meets all criteria as the pro-MMP-9 activator. HSC cultured in three-dimensional type-I collagen, but not in Matrigel, IL-1 induces expression of MMP-13 and its matured form at 50 and 25 kDa, respectively. In vitro reconstitution experiment proves that MMP-13, but not its zymogen, activates pro-MMP-9. Further, short hairpin RNA targeting MMP-13 abolishes pro-MMP-9 activation and HSC trans-differentiation. We further demonstrate that pro-MMP-13 activation is facilitated with a membrane-associated factor, inhibited with tissue inhibitor of metalloproteinase-2, and abolished with short hairpin RNA against MMP-14. Moreover, pro-MMP-13 is also activated by a secreted factor, which is absorbed by gelatin-Sepharose and reconstituted with MMP-9. Thus, IL-1-induced trans-differentiation of HSCs in three-dimensional extracellular matrix is facilitated by an MMP activation cascade (MMP-14 > MMP-13 > MMP-9) and a positive feedback loop of MMP-9 > MMP-13, suggesting their critical roles in liver injury and repair.
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